JP2021075574A - Method of repairing age and disease immune dysfunction and cellular senescence with lymphoid stem cells and method of re-applying those for therapeutic use - Google Patents

Abstract

To provide methods for treatment of diseases of ageing including immunosenescence, immune dysfunction, inflammation and impairment of early lymphoid lineage differentiation.SOLUTION: The invention relates to the use of granulocyte colony stimulating factors to assist in stem cell mobilization, optionally in combination with the application of a method of delivering precise magnetic field patterns which agree with the body's own natural magnetic field patterns, and further in combination with re-infusion of previously collected autologous cells and/or plasma, optionally including allogeneic (healthy donor) cells and blood plasma.SELECTED DRAWING: Figure 2

Description

This application is a priority benefit to US Provisional Application No. 61 / 821,319 filed May 9, 2013, and US Provisional Application No. 61 / 893,444 filed October 21, 2013. All of which are incorporated herein by reference in their entirety.

The present invention relates to methods for the treatment of diseases of aging, including immunosenescence, immune dysfunction, inflammation, and impaired early lymphoid differentiation. The present invention, more specifically, in combination with the application of a method of sending an accurate magnetic field pattern that matches the body's own natural magnetic field pattern as needed, and further, as needed, allogeneic (healthy donors). ) Concerning the use of granulocyte colony stimulators to aid stem cell recruitment in combination with previously harvested autologous cells and / or plasma reinjection, including cells and plasma.

A phenomenon that appears as growth arrest after a period of apparently normal cell proliferation is known as Replicative Senescence (RS). Replication aging is found in a) cells from adults of all ages, b) embryonic tissue, and c) animals.

Aging is associated with changes in the immune system, including disorders in innate immunity, T-lymphocyte production, and B-lymphocyte production, and these disorders are associated with immunosenescence and immune dysfunction in affected individuals. It contributes. Aging of pluripotent hematopoietic stem cells (HSCs) contributes to impaired early lymphoid lineage differentiation. Immune dysfunction, and immunosenescence due to increased inflammation, are aging and, for example, anemia, chronic disease, autoimmune deficiency, cancer, cardiovascular disease, infectious diseases, metabolic diseases, neurodegenerative diseases, protein energy malnutrition. It is the main cause of diseases such as weakness and weakness.

Oscillating magnetic fields have been used for many years in the process of giving physiotherapy to clinical patients suffering from fractures. These devices are commonly referred to as bone growth stimulators. Bone growth occurs as a result of stem cell stimulation, activation, and differentiation. However, the signals of these devices are a series of pulses or vibration waves that have symmetry typical of electronically generated signals (see "General Electronically Generated Signals" in FIG. 1). is there. More recently, researchers have discovered that the body emits its own complex electromagnetic field patterns. Unique patterns are associated with immunosenescence and immune dysfunction, stress, or disease. By capturing these anomalous patterns, restoring them, and re-entering them into the target patient, researchers find that the more natural biological patterns the patterns become, the more efficient the normal "therapeutic process" is. Establish the theory that it can be restored to.

What is unique about the described methods of the present disclosure is the fusion of these unique processes for disseminating treatments.

The number of Cumulative population doublings (CPDs) cells received during culture varies considerably between cell type and cell type. The initial results are that the relationships between CPDs cells are tolerable, and that the lifespan of the species from which the cells are derived is, for example, cells from the Galapagos tortoise that can live for centuries, and mouse cells divide approximately 15 times. On the other hand, it was suggested that it was tolerable so that it splits about 110 times. Cells taken from patients with progeria, such as Werner's syndrome (WS), show far less CPDs than normal people. Certain "immortalized" cell lines (eg, embryonic germ cells and most tumor-derived cell lines such as HeLa cells) can be isolated endlessly without reaching RS.

Biomarkers of cellular senescence include:
1) Growth arrest-senescent cells are growth arrested during the transition of the cell cycle from the G1 phase to the S phase. Growth arrest in RS is irreversible in that growth factors cannot stimulate and divide cells, even though senescent cells remain metabolically active for extended periods of time.
2) Cell morphology-senescent cells are larger and the senescent population has more diverse morphological types than early CPDs (normal human fibroblasts (left) and senescent morphology (three cells on the right). Note FIG. 12 showing blast cells). Note the general elongated morphology of senescent cells.
3) In aging-related β-galactosidase (SA β-gal) activity-in vitro (in vitro) and in vivo (in vivo), the proportion of cells positive for SA β-gal increased with respect to CPDs and age, respectively. To do. In immortalized cell lines such as HeLa tumor cells, the proportion of cells positive for SA β-gal does not correlate with CPDs. Also, an increase in SA β-gal correlates with the appearance of morphological forms of aging.
4) Ploidy increase-It has been shown that the proportion of polyploid cells, that is, the number of cells with three or more replicas of the chromosome, increases. Deletions in mitochondrial DNA (mtDNA) were also observed in at least some cells, both during RS and during in vivo aging.
5) Changes in gene expression levels-The expression levels of some genes change during in vitro cell senescence. One important type of gene overexpressed in senescent cells is an inflammatory regulator such as interleukin 6 (IL6). The pro-inflammatory proteins secreted by senescent cells that cause senescence may lead to a positive feedback loop and induction of senescence in normal cells close to senescent cells.
6) Metalloproteinase and heat shock protein production-Aged cells also show increased metalloproteinase activity to degrade extracellular matrix and decreased ability to express heat shock proteins.
7) Telomere shortening-a major cause of RS in human fibroblasts, which plays a major role in aging.

A phenomenon that manifests as growth arrest after a period of apparently normal cell proliferation is known as replication aging (RS). Replication aging is found in a) adult cells of all ages, b) embryonic tissue, and c) animals. The present invention discloses therapeutic methods for treating many diseases resulting from the aging phenomenon.

Aging is associated with changes in the immune system, including disorders in innate immunity, T-lymphocyte production, and B-lymphocyte production, and these disorders are associated with immunosenescence and immune dysfunction in affected individuals. It contributes. Aging of pluripotent hematopoietic stem cells (HSCs) contributes to impaired early lymphoid lineage differentiation. Immunosenescence with immune dysfunction and increased inflammation includes aging and anemia, chronic diseases, autoimmune deficiency, cancer, cardiovascular disease, infectious diseases, metabolic diseases, neurodegenerative diseases, protein energy malnutrition, and It is the main cause of diseases such as frailty.

Oscillating magnetic fields have been used for many years in the process of giving physiotherapy to clinical patients suffering from fractures. These devices are commonly referred to as bone growth stimulators. Bone growth occurs as a result of stem cell stimulation, activation, and differentiation. However, the signals of these devices are a series of pulses or vibration waves that have symmetry typical of electronically generated signals (see "General Electronically Generated Signals" in FIG. 1). is there. More recently, researchers have discovered that the body emits its own complex electromagnetic field patterns. Unique patterns are associated with immunosenescence and immune dysfunction, stress, or disease. By capturing these anomalous patterns, restoring them, and re-entering them into the target patient, researchers find that the more natural biological patterns the patterns become, the more efficient the normal "therapeutic process" is. Establish the theory that it can be restored to. U.S. Pat. No. 7,361,136, which belongs to Parker, describes treatment methods utilizing such devices, which are incorporated herein by reference in their entirety.

The methods of the present disclosure describe treatments that represent a set of one or more of these treatments.

Therefore, a main object of the present invention is an aging disease, immunity by using a stem cell mobilizing agent, G-CSF (Granulocyte Colony Stimulating Factor) in combination with one or more of the following: The purpose is to treat aging and aging disorders associated with immune dysfunction and inflammation, as well as disorders in early lymphoid differentiation.

Collect autologous stem cells and plasma using a cell collector;

Reinject previously collected autologous cells and / or plasma;

Reinject previously collected autologous cells with allogeneic (healthy donor) cells and / or plasma;

Reinject allogeneic (healthy donor) cells and / or plasma.

Using a method that sends an accurate magnetic field pattern that matches the body's own natural magnetic field pattern, aging diseases due to stem cell activation, and aging diseases with immune aging, immune dysfunction, and inflammation are routinely treated. An instrument that can be used for clinical treatment, one or more of the following is to be treated in combination with a stem cell mobilizer, G-CSF (Granulocyte Colony Stimulating Factor).

Autologous cells and plasma are collected using a cell collector and reinjected with previously collected autologous cells and / or plasma;

Reinject previously collected autologous cells and / or plasma with allogeneic (healthy donor) cells and / or plasma.

By using a method that sends an accurate magnetic field pattern that matches the body's own natural magnetic field pattern, aging diseases due to activation of stem cells, and aging diseases with immunosenescence, immune dysfunction, and inflammation are routinely treated. The subject is to treat in combination with allogeneic cells and / or plasma of healthy donors using instruments that can be used in clinical treatment.

By using a method that sends an accurate magnetic field pattern that matches the body's own natural magnetic field pattern, aging diseases due to activation of stem cells, and aging diseases with immunosenescence, immune dysfunction, and inflammation are routinely treated. The purpose of the treatment is to use a device that can be used in clinical treatment in combination with a stem cell mobilizer, G-CSF (Granulocyte Colony Stimulating Factor).

Routine aging disorders due to stem cell activation and aging disorders with immunosenescence, immune dysfunction and inflammation, using methods that deliver accurate magnetic field patterns that match the body's own natural magnetic field patterns. It is to treat with equipment that can be used in clinical treatment.

Using a method that sends an accurate magnetic field pattern that matches the body's own natural magnetic field pattern, aging diseases due to activation of stem cells, and aging diseases with immunosenescence, immune dysfunction, and inflammation are routinely treated. The subject is to treat in combination with autologous cells and / or plasma using instruments that can be used in clinical treatment.

Other objects and advantages of the present invention will become apparent from the following description, along with the accompanying drawings, with the drawings and examples of the present invention, specific embodiments. Any drawing contained herein constitutes a part of the present specification and includes exemplary embodiments of the present invention, showing their various purposes and features.

FIG. 1 is a diagram showing a general electronically generated signal.

FIG. 2 is a diagram showing the relationship between aging, immunosenescence, inflammation, and disease states.

FIG. 3 is a diagram showing the installation of SQUID at Vanderbilt University.

FIG. 4 is a diagram showing a complex biological waveform of nature existing in the body.

FIG. 5 is a diagram showing a natural complex biological waveform of a frog nerve.

FIG. 6 is a diagram showing concepts for extracting, analyzing, and deriving waveforms.

FIG. 7 is a diagram showing the generation of a magnetic field by an electric current.

FIG. 8 is a diagram showing the use of a solenoid design field generator.

FIG. 9 is a diagram showing a toroidal magnetic field applicator.

FIG. 10 is a diagram showing a Helmholtz coil field applicator.

FIG. 11 is a diagram showing a plane field applicator.

FIG. 12 is a diagram showing normal cell morphology of aging.

FIG. 13 shows the effect of the method of the invention on the regulation of levels of inflammatory and non-inflammatory markers in patient 1.

FIG. 14 shows the effect of the method of the invention on the regulation of levels of inflammatory and non-inflammatory markers in patient 2.

FIG. 15 shows the effect of the method of the invention on the regulation of levels of natural killer cells in patient 2.

FIG. 16 shows the effect of the method of the invention on the regulation of levels of inflammatory and non-inflammatory markers in patient 3.

FIG. 17 shows the effect of the method of the invention on the regulation of naive T cell levels in patient 4.

FIG. 18 shows the effect of the method of the invention on the regulation of levels of central memory T cell and natural killer cell activity in patient 4.

FIG. 19 shows the effect of the method of the invention on the regulation of naive T cell levels in patient 5.

FIG. 20 shows the effect of the method of the invention on the regulation of levels of central memory T cells in patient 5.

FIG. 21 shows the effect of the method of the invention on the regulation of levels of natural killer cell activity in patient 5.

FIG. 22 shows the effect of the method of the invention on the regulation of levels of natural killer cell activity in patient 6.

FIG. 23 shows the effect of the method of the invention on the regulation of levels of natural killer cell activity in patient 7.

FIG. 24 is a SPECT scan showing improvement in patients with neurodegenerative diseases after treatment according to the present invention.

FIG. 25 shows the effect of the method of the invention on the regulation of levels of natural killer cell activity in patient 8.

FIG. 26 shows the effect of the method of the invention on the regulation of total B cell levels in patient 9.

FIG. 27 shows the effect of the method of the invention on the regulation of memory T cell levels in patient 9.

FIG. 28 shows the effect of the method of the invention on the regulation of naive T cell levels in patient 9.

FIG. 29 shows the effect of the method of the invention on the regulation of levels of natural killer cell activity in patient 9.

Aging is associated with changes in the immune system, including disorders in innate immunity, T-lymphocyte production, and B-lymphocyte production, and these disorders contribute to immunosenescence in affected individuals.

Changes in the pluripotency of pluripotent hematopoietic stem cells (HSCs) have been causally linked to reduced lymphocyte production during aging in mice and humans. Whole-genome expression analysis showed that HSC-specific denaturation of gene expression contributed to this phenotype. Pools of HSCs contain different HSC subpopulations that are biased towards bone marrow or lymphatic differentiation. There is evidence that bone marrow biased HSCs are maintained but lymphatic biased HSCs are lost during aging. These result in an imbalance in bone marrow lymphocyte production resulting from aging. The molecular causes of this age-related selection of the HSC subpopulation have not yet been explained.

Accumulation of DNA damage is associated with aging of HSCs in both mice and humans. In addition, studies of telomerase knockout mice (Terc − / −) have shown that chronic DNA damage signaling in response to telomere dysfunction involves both cell-specific checkpoints and degeneration in the blood circulation environment in lymphocyte production. It revealed evidence that it leads to accelerated hematopoietic skewing with a strong decrease. HSC aging contributes to impaired early lymphoid differentiation. This process is associated with a selective increase in bone marrow competent HSCs and a decrease in lymphatic competent HSCs during aging. This age-related skew in the maintenance of the HSCs subpopulation contributes to deficiencies in lymphocyte production and impaired immune function during aging. Molecular mechanisms that can induce stem cell aging include DNA damage and accumulation of telomere dysfunction, with cell-specific checkpoints as well as degeneration of the stem cell environment (nitch and overall environment). It may contribute to the age-dependent choices of the population. Selective survival of different subpopulations of HSCs also contributes to the development of malignancies in the hematopoietic system, and selective maintenance of myelocompetent HSCs increases the risk of mutation accumulation in the bone marrow system, thereby increasing the risk of mutation accumulation. It leads to an increase in myeloproliferative disorders during aging. Loss of lymphocompetent HSCs can induce malignancies of lymphoid origin by impairing the growth competition of lymphocyte progenitor cells in the niche. Along these lines, its age-related disorders in the proliferation of hematopoietic progenitor cells have been shown to select the proliferation of malignant clones. In contrast to the potential effects on tumor promotion, reduction of the HSC subpopulation may play a role in the tumor suppression mechanism associated with the reduction of injured HSCs. The combination of cell surface markers allows human hematopoietic cells to be subdivided into different subpopulations and also during human aging into lymphoid and / or bone marrow competent subpopulations. A step-by-step process of lymphatic system differentiation of pluripotent hematopoietic stem cells (HSCs) in human bone marrow finds that CD10 + progenitor cells lack bone marrow and erythrocyte potential but can generate all lymphatic systems. Is hypothesized to begin with expression of the cell surface antigen CD10 (CALLA or MME) on CD34 + progenitor cells. However, subsequent studies have shown that CD34 +, CD10 + cells are relatively small T cells or natural, even without the expression of lineage markers (Lin-: CD3-, CD14-, CD15-, CD19-, CD56-, CD235a-). It has been shown to show a strong bias towards the potential of B cells as well as the potential of killer (NK) cells. CD34 +, Lin-, and CD10 + cells lacking expression of CD24 are precursors of the CD34 +, Lin-CD10 + CD24 + population, but nevertheless, with the expression of some B cell-specific genes, the B cell line. Show molecular evidence of involvement in. L-selectin (CD62L) is expressed on lymphocytes and mediates homing to peripheral lymphoid organs. Studies have reported that upregulation of CD62L expression on c-Kit + Lin-Sca-1 + mouse bone marrow cells correlates with reduced erythrocyte and megakaryocyte potential and effective thymic engraftment. In the progenitor cell hierarchy of lymphocyte involvement in human cells, the stage of initial lymphatic stimulation (priming) prior to CD10 expression or independently prior to involvement in the B lymphatic system has high expression of CD62L. It is a CD34 +, Lymph-, CD10-progenitor cell subpopulation of human bone marrow that lacks the potential of clonogenic bone marrow or erythrocytes. In stromal culture, these cells can produce B cells, NK cells, and T cells as well as monocytes and dendritic cells.

Aging is associated with changes in the immune system, including disorders in T-lymphocyte production and B-lymphocyte production, which contribute to immunosenescence in affected individuals. Immunosenescence with immune dysfunction and increased inflammation is associated with aging and chronic diseases of anemia, autoimmune deficiency, cancer, cardiovascular disease, infectious diseases, metabolic diseases, neurodegenerative diseases, and protein energy malnutrition. It is the main cause of such diseases.

Natural magnetic field waveforms have been discovered in relation to biological processes since the discovery and development of SQUID (“Installation of SQUID at Vanderbilt University” in FIG. 3). These waveforms appear in a complex pattern as shown in (“Natural complex biological waveforms present in the body” in FIG. 4).

There is nothing new about measuring and recording these waveforms, but the use of these waveforms in useful medical equipment has only recently been made possible by advances in modern electronics. Therefore, identification, extraction, and separation, and methods of transmitting their magnetic field patterns in a therapeutically effective manner are the main objectives of the present invention (see “Extraction, Analysis, and Derivation” in FIG. 6). ..

Since the late 1960s, researchers have theorized that magnetic field waveform information content is useful because it is received, recognized, and therapeutically effective by the body (if delivered in a particular way). There is. The modern bone growth stimulator is an example of such a device, which has proven to be useful in medical applications for promoting bone tissue repair and growth. It is necessary to theoretically prove that this method, and the device that transmits according to this method, is more effective in providing medical treatment to the patient.

Natural biological waveforms are measured in many body processes. Explanatory diagrams (“Natural Complex Biological Waveforms Found in the Body” in FIG. 4) describe some of these processes.
More recently, sophisticated and sensitive recording techniques have been used to record biological processes with greater sensitivity, such as firing a single nerve axon. Biological waveforms are also associated with specific disease and inflammatory processes that are mobilized from the bone marrow into the blood to reach the diseased site, causing activation of stem cells local to the diseased site. It is speculated that these waveforms are related to the body's natural therapeutic process. Researchers also speculate that external electromagnetic signals applied to the body are ignored unless:
• Harmful signals such as ionized signals (eg, X-rays) • Benign signals that affect the site of injury (eg, aging disease or aging disease with immunosenescence and immune dysfunction and inflammation)

The device proposed herein is to send a natural bio-waveform electromagnetic field to the site of injury, which is more effective than previously used signals in combination with methods of increasing the concentration of stem cells at the site of disease. To make it work. This method is the actual use of these waveforms in the generation and transmission of natural biological waveforms suitable for a particular injury.
Biological waveform capture, storage, and replication process

The whole process starts with the following items:
-Discovery of biological signals-Separation of repair signals-Preservation of repair signals-Generation of repair signals-Transmission of repair signals-Matching with specified protocols

Discovery of Biological Signals The process of this discovery begins with a known pathological condition. For example, cancer has a well-understood biological process that helps repair immune dysfunction and immunosenescence and inflammation during activity. All of these processes involve the generation and release of natural biological waveforms.

Therefore, this discovery is a high-sensitivity measuring device known as SQUID (Superconductive Quantum Interference Device) with a patient having a known state in order to detect and measure the condition waveforms. start from. This device, or a representative of the device, is shown in "Installation of SQUID at Vanderbilt University" in FIG. Waveforms produced by the body, or bioorganisms, have certain specific characteristics. An example of certain waveforms is shown in FIG. 5 "Natural Complex Biological Waveforms of Frog Nerves".

Measurements of natural biological waveforms due to the underlying pathological condition are facilitated by the SQUID apparatus. SQUID devices are routinely used to measure such waveforms. Conversely, the body can emit certain natural biological waveforms that are associated with normal biological function. That is, these waveforms are captured from healthy subjects.

Separation of Repair Signals The natural biometric waveforms of a patient's subject pathology and a patient's undamaged subject are expected to differ in certain characteristics. In fact, Romanian researchers report in a treatise that these signals actually exist and can be separated. The separation process can be performed by digitizing and analyzing their waveforms using pattern recognition, or other graphics techniques, and then performing some sort of digital operation on the pattern. Waveform separation
-Healthy subjects-A simple procedure by measuring subjects with aging diseases and subjects with aging diseases with immunosenescence, immune dysfunction, and inflammation.

Each measurement is captured, digitized using mechanical or electrical conversion means, and stored in a common file format. The procedure for further separating suspicious natural biological signals is the process of comparing two waveforms that produce "difference" waveforms (see "Extracting, Analyzing, and Derivation" on page 10), which contributes to the therapeutic process. Presented as a waveform.

The original source waveforms, such as the "disease" waveform and the "normal" waveform, are used as reference waveforms in studies comparing the relative effects of those waveforms on the "difference" waveform.

Restoration signal storage Subsequently, the final selected repair signal is stored in electronic format or in printed graphic format, generally in a digitized manner. It may use a common flat file (unstructured file) or relational database for electronic storage media.

(Generation of repair signal)
Subsequently, the stored electrical signal pattern is then regenerated by a device (here referred to as a modulator) that drives an external applicator. Regeneration of these electrical patterns is performed by the following method.
-Use the internal digital look-up table-Solve using the internal derivation equation-Use a series of signals as seen in the Fourier series Then, when the basic repair signal is regenerated, then generate Modulated by the device for:
-Frequency-Intensity-Duty Cycle Subsequently, this final signal is amplified and prepared for transmission to the patient or subject.

(Transmission of repair signal)
The repair signal has been captured, stored, processed, and modulated and is ready to be transmitted. Generally, as shown in FIG. 7, the magnetic field is transmitted by passing an electric current through various forms of wire loop assembly.
These types are
It may be a solenoid, a toroid, a flat (or flat) coil, or a Helmholtz coil.

The solenoid magnetic field pattern can be seen in "Use of Solenoid Design" in FIG. The toroidal magnetic field pattern can be seen in the "toroidal magnetic field applicator" of FIG. The design of the planar coil can be seen in the "plane field applicator" of FIG.
The Helmholtz design can be seen in the "Helmholtz coil field applicator" in FIG.

Before supplying current to the various types of applicators, the power of the modulator must amplify the stored signal to a level at which it can excite the coil. This amplification requires a power level consumption of up to 500 watts for linear amplification and can be significantly lower for switching-type (digital) designs.

Consistency with the specified protocol Consistency with the specified protocol requires specifying a particular type of step-by-step treatment procedure. These steps are usually
-Requires a predetermined time of exposure performed, a predetermined time between exposures, a predetermined exposure application amount, a predetermined application amount design, and a predetermined application amount duty cycle.

For example, the exposure performed will require a gradual exposure of 30 minutes, 60 minutes, or 90 minutes over several days. Exposure will be stepwise with a certain delay between each exposure. The application amount will be adjusted up and down according to the needs of the subject. The application amount design itself is specified according to the choice of one or several types of waveforms stored in the machine, and the application amount must be regulated according to the particular duty cycle.

Various embodiments of the present invention are shown in the following examples.

Example 1
This protocol uses granulocyte colony stimulator (g-csf) for stem cell recruitment and autologous stem cell-rich plasma to improve the level of anti-aging biomarkers in recipients. (Autologous stem cell rich (rich) plasma) will be used to evaluate the effectiveness of stem cell activation.

They will be administered G-CSF daily at a dose of 5-15 μg / kg, either intravenously or subcutaneously for 12 months, 5-7 days each month. Evaluations that measure anti-aging biomarkers and clinical markers of aging, as reported through a 13-item clinical evaluation, will be performed at baseline prior to the start of treatment. It will be repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Half of the recipients will be randomly selected for 12 months during the second 12-month study period, as they will also receive autologous stem cell-rich plasma in a fixed dose (alliquot) of 50 ml per month. become. Autologous plasma donors are also plasma recipients. Self-donors will receive G-CSF for 3 days before undergoing plasma exchange. This will stimulate a significantly increased number of stem cells in plasma.
The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Safety Assessment Baseline physical examination and blood chemistry will be performed on all recipients at baseline. These will be repeated 4 times after 3 months, 6 months, 9 months, and 12 months of treatment, and during the year following the end of the last treatment.

Safety and tolerance will be monitored through a series of reports of adverse events.

Example 2
This protocol uses granulocyte colony stimulating factor (G-CSF) to improve the levels of anti-aging biomarkers in recipients, with stem cell recruitment and autologous stem cell-rich plasma. The effectiveness of stem cell activation will be evaluated.

Patients will be treated with G-CSF stem cell recruitment, and autologous stem cell-rich plasma to improve the levels of anti-aging biomarkers in the recipient.

Primary Objective During treatment, the patient has levels of biomarkers of anti-aging in the recipient during one year of treatment and during one year of treatment after the end of treatment. Will continue to be evaluated for improvement.

Second objective: Improvement of clinical markers of aging as reported through 13 clinical evaluations

Study Design This study uses a long-term safe "drug"(G-CSF; autologous plasma; ergo Phase II), although the new method is (ergo Phase I). It is classified into Phase I / II.

They will be administered G-CSF daily at a dose of 5-15 μg / kg, either intravenously or subcutaneously for 12 months, 5-7 days each month. In the first 5-7 days, they will also be administered autologous stem cell-rich plasma in 50 ml aliquots each month for 12 months. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Self-donors will administer G-CSF for 5-7 days, either intravenously or subcutaneously, at a dose of 5-15 μg / kg for 3 days prior to plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel 2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 3
This protocol uses stem cell recruitment using granulocyte colony stimulator (G-CSF) to improve the level of anti-aging biomarkers in recipients and ABO-matched healthy cord blood. The effectiveness of stem cell activation will be evaluated in autologous stem cell-rich plasma combined with infused stem cell-rich plasma from allogeneic donors.

Patients have G-CSF stem cell recruitment to improve the level of anti-aging biomarkers in the recipient, and infused stem cell-rich plasma from ABO-matched healthy cord blood allogeneic donors. Will be treated with autologous stem cell-rich plasma in combination with.

Interested in assessing levels of anti-aging biomarkers, and from administration of G-CSF stem cell recruitment, as well as autologous stem cell-rich plasma, and ABO-matched healthy cord blood allogeneic donors Adults who will also receive infusions of stem cell-rich plasma will be treated monthly for a year to determine what improvements these markers have.

They will be administered G-CSF daily at a dose of 5-15 μg / kg, either intravenously or subcutaneously for 12 months, 5-7 days each month. In the first 5-7 days, they will also be administered autologous stem cell-rich plasma in 50 ml aliquots each month for 12 months. After completion of daily G-CSF for 5-7 days, they will also be administered allogeneic cord blood stem cell-rich plasma in 50 ml aliquots (alicoat) monthly for 12 months. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Self-donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma.

The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

Allogeneic umbilical cord blood plasma donor All donations of umbilical cord blood plasma are taken from the umbilical cord blood of healthy infants collected from the placenta delivered at birth and normally discarded, and its stem cells are collected at a later date , Is to be stored cold (frozen) for personal use by babies.

The expected plasma yield from cord blood is about 55 ml. Plasma is divided into 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated.

Based on the average prevalence of ABO types, the number of donors required is expected to be approximately 12-15 per recipient.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 4
Recipients (recipients) mobilize G-CSF stem cells and inject from ABO-matched healthy allogeneic donors to improve the level of anti-aging biomarkers in the recipients. It will be treated with autologous stem cell-rich plasma in combination with stem cell-rich plasma.

Interested in assessing levels of anti-aging biomarkers, not only administration of G-CSF stem cell recruitment, but also autologous stem cell-rich plasma, and stem cell-rich plasma from ABO-compatible healthy allogeneic donors Recipients who will also receive plasma infusions will be treated monthly for a year to determine what improvements are in those markers. I).

They will be administered G-CSF daily at a dose of 5-15 μg / kg, either intravenously or subcutaneously for 12 months, 5-7 days each month. In the first 5-7 days, they will also be administered autologous stem cell-rich plasma in 50 ml aliquots each month for 12 months. After completion of daily G-CSF for 5-7 days, they will also be administered allogeneic stem cell-rich plasma in 50 ml aliquots (alicoat) monthly for 12 months. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Self-donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

The other groups that make up the Allogeneic Stem Cell Rich Plasma Donor Research Population are allogeneic plasma donors. Donors will be administered G-CSF at a dose of 5-15 μg / kg, either intravenously or subcutaneously, for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. Donors will undergo repeated infection tests on the day of exchange therapy (ferresis).

The expected plasma yield from exchange therapy (ferresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated. Donors are limited to men and heifers to avoid the presence of cytotoxic lymphocytes and granulocyte antibodies.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 5
This protocol uses stem cell recruitment using granulocyte colony stimulating factor (G-CSF) to improve the levels of anti-aging biomarkers in recipients and ABO-matched health allogeneic. In combination with infused stem cell-rich plasma from line donors, the effectiveness of stem cell activation will be evaluated.

Patients will be treated in combination with G-CSF stem cell recruitment and infused stem cell-rich plasma from ABO-matched healthy allogeneic donors for anti-aging biotechnology in the recipient. Improvements in marker level will be monitored.

Recipes interested in assessing biomarker levels of anti-aging and willing to accept administration of G-CSF stem cell recruitment and infusion of stem cell-rich plasma from ABO-matched healthy allogeneic donors Ent (recipients) will be treated monthly for a year to determine what improvements these markers have. Recipients will be administered G-CSF daily for 12 months, 5-7 days each month, either intravenously or subcutaneously at a dose of 5-15 μg / kg. .. After completion of daily G-CSF for 5-7 days, they will also be administered allogeneic stem cell-rich plasma in 50 ml aliquots (alicoat) monthly for 12 months. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Allogeneic stem cell-rich plasma donors Donors will be administered G-CSF intravenously or subcutaneously at doses of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. The expected plasma yield from exchange therapy (ferresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated. Donors are limited to men and heifers to avoid the presence of cytotoxic lymphocytes and granulocyte antibodies.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 6
This protocol uses stem cell recruitment using granulocyte colony-stimulating factor (G-CSF) to improve the levels of anti-aging biomarkers in recipients and ABO-matched health allogeneic. Autologous stem cell-rich plasma combined with infused stem cell-rich plasma from line donors will be used to evaluate the effectiveness of stem cell activation.

Patients hope to improve levels of anti-aging biomarkers in recipients, G-CSF stem cell recruitment, and infused stem cell rich from ABO-matched healthy allogeneic donors It will be treated with autologous stem cell-rich plasma in combination with plasma.

Interested in assessing levels of anti-aging biomarkers, not only administration of G-CSF stem cell recruitment, but also autologous stem cell-rich plasma, and stem cell-rich plasma from ABO-compatible healthy allogeneic donors Recipients who will also receive plasma infusions will be treated monthly for a year to determine what improvements are in those markers.
Recipients will be administered G-CSF daily for 12 months, 5-7 days each month, either intravenously or subcutaneously at a dose of 5-15 μg / kg. .. In the first 5-7 days, they will also be administered autologous stem cell-rich plasma in 50 ml aliquots each month for 12 months. After completion of daily G-CSF for 5-7 days, they will also be administered allogeneic stem cell-rich plasma in 50 ml aliquots (alicoat) monthly for 12 months. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Self-donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

Allogeneic stem cell-rich plasma donors Donors will administer G-CSF intravenously or subcutaneously at doses of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. The expected plasma yield from exchange therapy (ferresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated. Donors are limited to men and heifers to avoid the presence of cytotoxic lymphocytes and granulocyte antibodies.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 7
This protocol uses granulocyte colony-stimulating factor (G-CSF) for stem cell recruitment, ABO-matched cord blood allogeneic, to improve the level of anti-aging biomarkers in recipients. In combination with infused stem cell-rich plasma from line donors, the effectiveness of stem cell activation will be evaluated.

Patients will be treated in combination with G-CSF stem cell recruitment, infused stem cell-rich plasma from ABO-matched cord blood allogeneic donors, and anti-aging biotechnology in the recipient. It will improve the level of the marker.

Interested in assessing biomarker levels of anti-aging and intending to receive stem cell-rich plasma infusions from ABO-matched cord blood allogeneic donors as well as administration of G-CSF stem cell recruitment. Recipients will be treated monthly for a year to determine what improvements these markers have.

Recipients will be administered G-CSF daily at doses of 5-15 μg / kg, either intravenously or subcutaneously, for 5-7 days of each month. After completion of daily G-CSF for 5-7 days, they will be administered allogeneic cord blood stem cell-rich plasma in 50 ml aliquots monthly for 12 months. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Umbilical Cord Blood Plasma Donors All donations of umbilical cord blood plasma are taken from plasma extracted from and normally discarded from healthy infant umbilical cord blood collected from the placenta delivered at birth, and its stem cells are later collected from the infant's It is to be stored at low temperature (frozen) for personal use. The expected plasma yield from cord blood is about 55 ml. Plasma is divided into about 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 8
This protocol changes the recipient's own natural magnetic field pattern to granulocyte colony-stimulating factor (G) in order to improve the level of anti-aging biomarkers in the recipient. -CSF) will be used in combination with stem cell recruitment and autologous stem cell-rich plasma to assess the effectiveness of stem cell activation.

Patients are required to improve the level of anti-aging biomarkers in the recipient and the clinical markers of aging as reported through a 13-item clinical evaluation of the correct natural magnetic field. In combination with application, it will be treated with G-CSF stem cell recruitment and autologous stem cell rich plasma.

Interested in assessing biomarker levels of anti-aging, not only administration of G-CSF stem cell recruitment, but also autologous stem cell-rich plasma, and the exact natural of the recipient itself. Recipients who will also be subject to magnetic field applications will be treated monthly for a year to determine what improvements these markers have.

Recipients will be administered G-CSF daily for 12 months, 5-7 days each month, either intravenously or subcutaneously at a dose of 5-15 μg / kg. .. In the early 5-7 days, they also had autologous stem cell-rich plasma in 50 ml aliquots each month for 12 months, with an accurate magnetic field pattern consistent with their body's own natural magnetic field pattern. Will be accepted. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Self-donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 9
This protocol changes the recipient's own natural magnetic field pattern to granulocyte colony-stimulating factor (G) in order to improve the level of anti-aging biomarkers in the recipient. -CSF) will be used in combination with stem cell recruitment and autologous stem cell-rich plasma in combination with infused stem cell-rich plasma from ABO-compatible healthy allogeneic donors to assess the effectiveness of stem cell activation.

Patients have G-CSF stem cell recruitment and ABO-compatible healthy allogeneic, in combination with the application of accurate natural magnetic fields to improve the level of anti-aging biomarkers in the recipient. It will be treated with autologous stem cell-rich plasma in combination with infused stem cell-rich plasma from an allogeneic donor.

Interested in assessing the level of anti-aging biomarkers, not only administration of G-CSF stem cell recruitment, but also autologous stem cell-rich plasma, stem cell-rich plasma from ABO-compatible healthy allogeneic donors injection, and 1 year, every month, the recipient (recipient) itself of the exact nature of the magnetic field also receive the intention of the recipient application (recipient) is, to determine whether there is any improvement in those markers Therefore, it will be treated. Recipients will be administered G-CSF daily for 12 months, 5-7 days each month, either intravenously or subcutaneously at a dose of 5-15 μg / kg. .. In the early 5-7 days, they also had autologous stem cell-rich plasma in 50 ml aliquots each month for 12 months, with an accurate magnetic field pattern consistent with their body's own natural magnetic field pattern. Will be accepted. After completion of daily G-CSF for 5-7 days, they will also be administered allogeneic stem cell-rich plasma in 50 ml aliquots (alicoat) monthly for 12 months. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points.

Self-donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

Allogeneic stem cell-rich plasma donors Allogeneic plasma donors are healthy, young adults (age 30 years or younger) without major medical diagnosis. Physical examination and standard blood chemistry and CBC will determine their eligibility. ABO / Rh type, hemoglobin dysfunction tests, and antibody panels are performed on each donor as well as infectious disease tests. Donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. Donors will undergo repeated infection tests on the day of exchange therapy (ferresis). The expected plasma yield from exchange therapy (ferresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated. Donors are limited to men and heifers to avoid the presence of cytotoxic lymphocytes and granulocyte antibodies.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation. Baseline physical examination and blood chemistry will be performed on all recipients at baseline. These are repeated 3 months, 6 months, 9 months, and 12 months after treatment and are repeated quarterly for the year following the end of treatment.

Example 10
This protocol combines natural magnetic field patterns with infused stem cell-rich plasma from ABO-matched healthy allogeneic donors to improve the level of anti-aging biomarkers in recipients. Will be used to evaluate the effectiveness of stem cell activation.

Recipients have stem cell recruitment in combination with the application of accurate natural magnetic fields to improve the levels of anti-aging biomarkers in plasma recipients. It will be treated with plasma from healthy allogeneic donors.

Interested in assessing biomarker levels of anti-aging, intending to receive donor plasma and having an accurate magnetic field pattern that matches their body's own natural magnetic field pattern on the same day Adults who are willing to accept will be treated monthly for a year to determine what improvements these markers have. Recipients will be administered ABO / Rh crossmatch plasma in 50 ml aliquots each month for 12 months. On the same day, they will accept the application of an accurate natural magnetic field. Evaluations to measure biomarkers will be performed at baseline and every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. In addition, clinical markers (13 groups) will be collected at their same time point.

Plasma donors All donors are healthy, young adults (age 30 years or younger) without major medical diagnosis. Physical examination and standard blood chemistry and CBC will determine their eligibility. ABO / Rh type and antibody panels are performed on each donor as well as infectious disease testing. Donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. Donors will undergo repeated infection tests on the day of exchange therapy (ferresis). The expected plasma yield from exchange therapy (ferresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated. Donors are limited to men and heifers to avoid the presence of cytotoxic lymphocytes and granulocyte antibodies.

Recipients have serious medical problems that would be contraindicated by injecting donor plasma and applying an accurate magnetic field pattern that matches their body's own natural magnetic field pattern. It can be of any age or gender. This is determined by physical examination and standard blood chemistry and CBC. Those ABO / Rh types will also be tested.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits between baseline and physical examinations that will provide second efficacy data for evaluation. Baseline physical examination, blood chemistry, and infection markers will be performed at baseline for all plasma donors and recipients. These are repeated 3 months, 6 months, 9 months, and 12 months after treatment, apart from infection markers, and are repeated quarterly for the year following the end of treatment.

Example 11
This protocol introduces natural magnetic field patterns to improve levels of anti-aging biomarkers in recipients, infused stem cell-rich plasma from ABO-matched healthy cord blood allogeneic donors. Will be used in combination with to evaluate the effectiveness of stem cell activation.

Recipients, in combination with the application of accurate natural magnetic fields, to improve the levels of anti-aging biomarkers in plasma recipients, healthy cord blood allogeneic It will be treated with plasma from a heterologous donor.

Interested in assessing biomarker levels of anti-aging, intending to receive cord blood donor plasma, and an accurate magnetic field that matches their body's own natural magnetic field pattern on the same day Recipients who intend to accept the pattern will be treated monthly for a year to determine what improvements are in those markers.

Recipients will be administered ABO / Rh crossmatch cord blood plasma in 50 ml aliquots each month for 12 months. On the same day, they will accept the application of an accurate natural magnetic field. Evaluations to measure biomarkers will be performed at baseline and every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. In addition, clinical markers will be collected at those same time points.

All donations of umbilical cord blood plasma are taken from plasma extracted from the umbilical cord blood of healthy babies collected from the placenta delivered at birth and normally discarded, and the stem cells are used for personal use by the baby at a later date. It is supposed to be stored at low temperature (frozen). The baby and mother do not have a major medical diagnosis, and the mother will sign a consent statement and agree to provide cord blood plasma. Physical examination and standard blood chemistry and CBC will determine their eligibility. ABO / Rh type and antibody panels are performed on each donor as well as infectious disease testing.

The expected plasma yield from cord blood is about 55 ml. Plasma will be divided into 50 ml dose aliquots and 5 ml test aliquots (for crossmatching). The sample will be frozen until the same ABO / Rh type plasma recipient is being treated. Based on the average prevalence of ABO types, the number of donors required is expected to be approximately 12-15 per recipient.

Recipients have serious medical problems that would be contraindicated by injecting donor plasma and applying an accurate magnetic field pattern that matches their body's own natural magnetic field pattern. It can be of any age or gender. This is determined by physical examination and standard blood chemistry and CBC. Those ABO / Rh types will also be tested.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18
There are also clinical markers (13 groups) evaluated on quarterly visits between baseline and physical examinations that will provide second efficacy data for evaluation. Baseline physical examination, blood chemistry, and infection markers will be performed at baseline for all plasma donors and recipients. These are repeated 3 months, 6 months, 9 months, and 12 months after treatment, apart from infection markers, and are repeated quarterly for the year following the end of treatment.

Example 12
This protocol changes the recipient's own natural magnetic field pattern to granulocyte colony-stimulating factor (G) in order to improve the level of anti-aging biomarkers in the recipient. -CSF) will be used in combination with stem cell recruitment to assess the effectiveness of stem cell activation.

Patients will be treated with G-CSF stem cell recruitment in combination with the application of accurate natural magnetic fields to improve the level of anti-aging biomarkers in the recipient. Become.

It is interested in assessing the level of a biomarker of the anti-aging (anti-aging), administration of G-CSF stem cell mobilization, and recipient (recipient) own exact nature of the magnetic field recipes going subject to the Receptors will be treated monthly for a year to determine what improvements these markers have.
Recipients will be administered G-CSF daily for 12 months, 5-7 days each month, either intravenously or subcutaneously at a dose of 5-15 μg / kg. .. On the same day, they will also accept an exact magnetic field pattern that matches the natural magnetic field pattern of their bodies themselves. Evaluations to measure biomarkers are performed at baseline prior to the start of treatment and are repeated every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. Will be. In addition, clinical markers will be collected at those same time points. All recipients receive G-CSF stem cell mobilization using routine clinical treatment and instruments that can assess their response, and the recipient's own nature. We do not have a significant medical diagnosis that excludes them from the application of accurate natural magnetic patterns that match their magnetic patterns. Physical examination, standard blood chemistry, CBC, and hemoglobin dysfunction tests will be done.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation. Baseline physical examination and blood chemistry will be performed on all recipients at baseline. These are repeated 3 months, 6 months, 9 months, and 12 months after treatment and are repeated quarterly for the year following the end of treatment.

Example 13
This protocol evaluates the effectiveness of stem cell activation using the recipient's own natural magnetic field pattern to improve the level of anti-aging biomarkers in the recipient. Will be done.

Recipients will be treated by the application of accurate natural magnetic fields to improve the levels of anti-aging biomarkers.

Assessment of improved levels of anti-aging biomarkers in the recipient during treatment for one year and one year after the end of treatment. Recipients who are interested in assessing the levels of anti-aging biomarkers and intend to receive G-CSF stem cell recruitment using accurate natural magnetic fields are those. It will be treated monthly for a year to determine what improvements the markers have. Recipients will accept an accurate magnetic field pattern that matches their body's own natural magnetic field pattern every month for 12 months. Evaluations to measure biomarkers will be performed before and thereafter every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. .. In addition, clinical markers will be collected at those same time points.
All recipients utilize routine clinical treatments and instruments that can assess their response to ensure accurate natural magnetic patterns that match the recipient's own natural magnetic patterns. They do not have a serious medical diagnosis that excludes them from the acceptance of magnetic patterns. Physical examination and standard blood chemistry, CBC, will determine their eligibility.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated with a quarterly visit between baseline and a physical examination that will provide second efficacy data for evaluation. Baseline physical examination, blood chemistry, and biomarkers will be performed on all recipients at baseline. These are repeated 3 months, 6 months, 9 months, and 12 months after treatment and are repeated quarterly for the year following the end of treatment.

Example 14
This protocol uses the recipient's own magnetic field pattern in combination with injected autologous stem cell-rich plasma to improve the level of anti-aging biomarkers in the recipient. Therefore, the effectiveness of stem cell activation will be evaluated.

Recipients have stem cell recruitment in combination with the application of accurate natural magnetic fields to improve the level of anti-aging biomarkers in recipients. It will be treated with autologous stem cell-rich plasma from the ent (recipient). Assessment of improved levels of anti-aging biomarkers in the recipient during treatment for one year and one year after the end of treatment. Recipients who are interested in assessing the levels of anti-aging biomarkers and intend to receive autologous stem cell rich donor plasma, what improvements are there in those markers? It will be treated monthly for a year to determine if it is.

Receptors will be administered autologous stem cell-rich plasma monthly in 50 ml aliquots for 12 months. On the same day, they will also accept an exact magnetic field pattern that matches the natural magnetic field pattern of their bodies themselves. Evaluations to measure biomarkers will be performed every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. In addition, clinical markers will be collected at those same time points.

Not all self-donors who are also recipients have a significant medical diagnosis that excludes them from receiving stem cell mobilization. Physical examination and standard blood chemistry, CBC, and infectious disease marker tests will determine their eligibility. Those ABO / Rh types will also be tested.

Donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. Donors will undergo repeated infection tests on the day of exchange therapy (ferresis). The ABO / Rh type will also be inspected.

The expected yield of stem cell-rich plasma from exchange therapy (feresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots and 5 ml test aliquots. The sample will be frozen until the same plasma recipient is being treated.

Applying an accurate natural magnetic field that matches the recipient's own natural magnetic field pattern, utilizing routine clinical treatment use and instruments capable of assessing the response.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.
Baseline physical examination, blood chemistry, and infection markers will be performed at baseline for all plasma donors and recipients. These are repeated 3 months, 6 months, 9 months, and 12 months after treatment, apart from infection markers, and are repeated quarterly for the year following the end of treatment.

Example 15
This protocol assesses the effectiveness of infused stem cell-rich plasma from ABO-matched healthy donors to improve the levels of anti-aging biomarkers in the recipient. Recipients are treated with plasma from healthy donors with stem cell recruitment to improve the levels of anti-aging biomarkers in plasma recipients. It will be.

Interested in assessing the levels of anti-aging biomarkers, recipients who intend to receive donor plasma will see what improvements these markers have. It will be treated monthly for a year to confirm.

Recipients will be administered ABO / Rh crossmatch plasma in 50 ml aliquots each month for 12 months. Evaluations to measure biomarkers will be performed every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. In addition, clinical markers will be collected at those same time points.

All donors are healthy, young adults (age 30 and younger) without major medical diagnosis. Physical examination and standard blood chemistry and CBC will determine their eligibility. ABO / Rh type and antibody panels are performed on each donor as well as infectious disease testing.

Donors will administer G-CSF intravenously or subcutaneously at a dose of 5-15 μg / kg for 3 days prior to undergoing plasmapheresis. This will stimulate a significantly increased number of stem cells in plasma. Donors will undergo repeated infection tests on the day of exchange therapy (ferresis).

The expected plasma yield from exchange therapy (ferresis) is about 2 liters. Plasma will be divided into about 36 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated. Donors are limited to men and heifers to avoid the presence of cytotoxic lymphocytes and granulocyte antibodies.

Receptors can be of any age or gender, as long as they do not have significant medical problems that would be contraindicated by injecting donor plasma. This is determined by physical examination and standard blood chemistry and CBC. Those ABO / Rh types will also be tested.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.
Baseline physical examination, blood chemistry, and infection markers will be performed at baseline for all plasma donors and recipients. These are repeated 3 months, 6 months, 9 months, and 12 months after treatment, apart from infection markers, and are repeated quarterly for the year following the end of treatment.

Example 16
This protocol assesses the effectiveness of infused stem cell-rich plasma from ABO-matched cord blood donors to improve the level of anti-aging biomarkers in recipients.

Recipients will be treated with plasma from cord blood donors to improve the levels of anti-aging biomarkers in plasma recipients. Assessment of improved levels of anti-aging biomarkers in the recipient during treatment for one year and one year after the end of treatment.
Improvement of clinical markers of aging as reported through a 13-item clinical evaluation.

Interested in assessing the levels of anti-aging biomarkers, recipients who intend to receive donor plasma for one year, monthly, what improvements to those markers Will be treated to determine if there is.

Recipients will be administered ABO / Rh crossmatch cord blood plasma in 50 ml aliquots each month for 12 months. Evaluations to measure biomarkers will be performed every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. In addition, clinical markers will be collected at those same time points.

All donations of umbilical cord blood plasma are taken from plasma extracted from the umbilical cord blood of healthy babies collected from the placenta delivered at birth and normally discarded, and the stem cells are used for personal use by the baby at a later date. It is supposed to be stored at low temperature (frozen). The baby and mother do not have a major medical diagnosis, and the mother will sign a consent statement and agree to donate plasma. Physical examination and standard blood chemistry and CBC will determine their eligibility. ABO / Rh type and antibody panels are performed on each donor as well as infectious disease testing. The expected plasma yield from cord blood is about 55 ml. Plasma will be divided into about 50 ml dose aliquots (for crossmatching) and 5 ml test aliquots. The sample will be frozen until the same ABO / Rh type plasma recipient is being treated.

Receptors can be of any age or gender, as long as they do not have significant medical problems that would be contraindicated by injecting donor plasma. This is determined by physical examination and standard blood chemistry and CBC. Those ABO / Rh types will also be tested.

There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Example 18
This protocol assesses the effectiveness of G-CSF (granulocyte colony stimulating factor) recruitment of CD34 + peripheral blood stem cells to improve the level of anti-aging biomarkers in the recipient. To do.

Patients will be treated with stem cell mobilization factors to improve the level of anti-aging biomarkers in the recipient. Assessment of improved levels of anti-aging biomarkers in the recipient during treatment for one year and one year after the end of treatment. Improvement of clinical markers of aging as reported through a 13-item clinical evaluation.

Recipients who are interested in assessing the levels of anti-aging biomarkers and intend to receive G-CSF stem cell mobilization for one year, what are those markers? It will be treated to determine if there is any improvement.

Recipients will be administered one cycle of G-CSF mobilization initially in 3 cycles and then in 3 months, 6 months, 9 months, and 12 months. In each cycle, G-CSF was administered intravenously or subcutaneously per day at a dose of 5 to 15 μg / kg daily for 3 to 7 days, followed by 7 days without G-CSF. Next, it consists of evaluation on 3 days out of 7 days off. Evaluations to measure biomarkers will be performed every 3 months during the treatment period and every 3 months for an additional 12 months after the end of the treatment period. In addition, clinical markers will be collected at those same time points.

Recipients who sign the consent statement can be of any age or gender, as long as they do not have significant medical problems that would be contraindicated by subcutaneous administration of G-CSF. This is determined by physical examination and standard blood chemistry and CBC. The hemoglobin dysfunction screen will also be tested. There are measurements of eight major biomarkers evaluated at baseline and after 3 months, 6 months, 9 months, and 12 months of treatment. These identical assessments will be continued every 3 months for additional years to examine the long-term effects of treatment. These evaluations are as follows:
1. 1. Immunosenescence panel
2. CCL 11
3. 3. Growth factors for TGFβ1 4. Intrinsic Factor Kappa Beta (NFκB)
5. DHEA-S
6. Plasma insulin 7. Telomere length 8. Cytokine Multiplex 18

There are also clinical markers (13 groups) evaluated on quarterly visits during physical examinations that will provide second efficacy data for evaluation.

Several patients were treated according to the protocol described in Example 18. These patients, their condition, and treatment are outlined with reference to FIGS. 13-19.

See FIG. 13 for patient 1.

Diagnosis: anemia, chronic disease (chronic obstructive pulmonary disease), cardiovascular disease (chronic heart failure), protein energy malnutrition, and frailty.

According to the basic protocol outlined in Example 18, patient MRs were treated with the stem cell mobilization factor, G-CSF, to improve the levels of anti-aging biomarkers in patients. During treatment, levels of anti-inflammatory (IL-10) and inflammatory (TNF-α) aging biomarkers were evaluated. Improved levels of IL-10, a clinical marker of aging, have been reported. Three months after treatment with G-CSF administered to the patient as in Example 18, IL-10 levels improved from 4.54 to 9.489.

An evaluation of improved levels of inflammatory aging biomarkers during treatment was made. Decreased levels of TNF-α, an inflammatory clinical marker of aging, have been reported. Three months after treatment with G-CSF administered to the patient as in Example 18, TNF-α levels went from 20.636 to 9.997.

While not wanting to be bound by any particular principle of action, a decrease in TNF-α and an increase in IL-10 results in anemia, chronic disease (chronic obstructive pulmonary disease), cardiovascular disease. It improved the clinical manifestations of disease (chronic heart failure), protein energy malnutrition, frailty-related inflammation and immunosenescence.

See FIGS. 14 and 15 for patient 2.

Diagnosis: cancer, protein energy malnutrition, weakness.

According to the basic protocol outlined in Example 18, patient DP was treated with the stem cell mobilization factor, G-CSF, to improve the level of biomarkers of aging in patients. During treatment, evaluation of biomarker levels of anti-inflammatory (IL-10) and inflammatory (TNF-α) aging was performed. An improved level of clinical markers of aging, IL-10, was reported. Three months after treatment with G-CSF administered to the patient as in Example 18, IL-10 levels improved from 1.787 to 5.774.

An evaluation of improved levels of inflammatory aging biomarkers during treatment was made. Decreased levels of TNF-α, an inflammatory clinical marker of aging, have been reported. Three months after treatment with G-CSF administered to the patient as in Example 18, TNF-α levels decreased from 11.072 to 7.243. Three months after treatment with G-CSF administered to the patient as in Example 18, the level of natural killer cells increased from 82 to 183.

While not wanting to be bound by any particular principle of action, a decrease in TNF-α and an increase in IL-10, and natural killer cells result in cancer, protein-energy malnutrition, and frailty. Improved clinical symptoms of associated inflammation and immunosenescence.

See FIG. 16 for patient 3.

Diagnosis: Chronic disease, neurodegenerative disease, frailty.

According to the basic protocol outlined in Example 18, patient JB was treated with the stem cell mobilization factor, G-CSF, to improve the level of biomarkers of aging in patients. During treatment, evaluation of biomarker levels of anti-inflammatory (IL-10) and inflammatory (TNF-α) aging was performed. Improved levels of IL-10, a clinical marker of aging, have been reported. Three months after treatment with G-CSF administered to the patient as in Example 18, IL-10 levels improved from 4.326 to 6.264.

An evaluation of improved levels of inflammatory aging biomarkers during treatment was made. Decreased levels of TNF-α, an inflammatory clinical marker of aging, have been reported. Three months after treatment with G-CSF administered to the patient as in Example 18, TNF-α levels decreased from 9.469 to 3.832.

While not wanting to be bound by any particular principle of action, a decrease in TNF-α and an increase in IL-10 results in chronic, neurodegenerative, weakness-related inflammation and immunosenescence. The clinical symptoms of the patient were improved.

See FIGS. 17 and 18 for patient 4.

Diagnosis: Chronic metabolic disease, type 2 diabetes, frailty.

According to the basic protocol outlined in Example 18, patient RA was treated with the stem cell mobilization factor, G-CSF, to improve the level of biomarkers of aging in patients. During treatment, improved levels of biomarkers of aging, immunosenescence, immune dysfunction, and early lymphoid differentiation were evaluated. Improvements by increasing levels of naive CD4 and CD8 and decreasing memory CD4T cells, as well as improved natural killer cell activity were reported. Two months after treatment with G-CSF administered to the patient as in Example 18, naive CD4 levels improved from 4.88 to 12.46. The level of naive CD8 improved from 14.62 to 24.17.

Evaluation of improvement observed a decrease in the level of memory CD4T cells from 80.37 to 68.52.

Also, an improvement in natural killer cell activity was reported 2 months after treatment with G-CSF administered to the patient as in Example 18, with levels of natural killer cell activity CD4 ranging from 9.46 to 18.36. Improved.

While not wanting to be bound by any particular principle of action, a decrease in central memory T cells and an increase in naive T cell and natural killer cell activity results in chronic metabolic disease, type 2 diabetes. , And improved clinical symptoms of weakness-related immune dysfunction, immunosenescence, and early lymphoid differentiation disorders.

See FIGS. 19-20 for patient 5.

Diagnosis: Chronic disease, cancer (Waldenström (type) macroglobulinemia), neurodegenerative disease (peripheral neuropathy), weakness.

According to the basic protocol outlined in Example 18, patient DS was treated with the stem cell mobilization factor, G-CSF, to improve the level of biomarkers of aging in patients. During treatment, improved levels of biomarkers of aging, immunosenescence, immune dysfunction, and early lymphoid differentiation were evaluated. Improvements by increasing naive CD4 levels and decreasing memory CD4T cells and improved natural killer cell activity were reported. Two months after treatment with G-CSF administered to the patient as in Example 18, naive CD4 levels improved from 12.08 to 42.47.

An assessment of the improvement in immune dysfunction further observed a decrease in the level of memory CD4T cells, which decreased from 78.09 to 40.90.

In addition, improvement in natural killer cell activity was reported. Two months after treatment with G-CSF administered to the patient as in Example 18, the level of natural killer cell active CD4 improved from 1.93 to 7.22.

While not wanting to be bound by any particular principle of action, a decrease in central memory T cells and an increase in naive T cell and natural killer cell activity results in chronic disease, cancer (Walden). Improvements in clinical manifestations of immune dysfunction, immunosenescence, and early lymphoid differentiation disorders associated with Ström's (type) macroglobulinemia), neurodegenerative diseases (peripheral neuropathy), and weakness.

See FIG. 22 for patient 6.

Diagnosis: Chronic disease, chronic infection (Lyme disease), neurodegenerative disease.

According to the basic protocol outlined in Example 18, patient SH was treated with the stem cell mobilization factor, G-CSF, to improve the level of biomarkers of aging in patients. During treatment, improved levels of biomarkers of aging, immunosenescence, and immune dysfunction were evaluated. Improvements by increasing levels of natural killer cells have been reported. Two months after treatment with G-CSF administered to the patient as in Example 18, the level of natural killer cells improved from 268 to 623.

While not wanting to be bound by any particular principle of action, the increase in natural killer cells results in immune function associated with chronic diseases, chronic infections (Lyme disease), and neurodegenerative diseases. Improvement of clinical symptoms of disorder and immunosenescence.

See FIGS. 23 and 24 for patient 7.

Diagnosis: Chronic disease, chronic fatigue syndrome, neurodegenerative disease, autoimmune disease (type 1 diabetes).

According to the basic protocol outlined in Example 18, patient LS was treated with the stem cell mobilization factor, G-CSF, to improve the level of biomarkers of aging in patients. During treatment, an assessment of improved levels of biomarkers of aging, immunosenescence, and immune dysfunction was performed. Improvements by increasing levels of natural killer cells have been reported. Two months after treatment with G-CSF administered to the patient as in Example 18, the level of natural killer cells improved from 47 to 120.

Two months after treatment with G-CSF administered to the patient as in Example 18, SPECT (single photon emission tomography) scan (FIG. 24) showed improvement in the patient's neurodegenerative disease.

Two months after treatment with G-CSF administered to the patient as in Example 18, the patient's insulin requirement for type 1 diabetes was reduced by 50%.

While not wanting to be bound by any particular principle of action, natural killer cell proliferation, SPECT scan results are associated with chronic disease, chronic fatigue syndrome, neurodegenerative disease and type 1 diabetes, immunity It showed improvement in clinical symptoms of dysfunction and immunosenescence.

See FIG. 25 for patient 8.

Diagnosis: Chronic disease, chronic viral infection.

According to the basic protocol outlined in Example 18, patient BF was treated with the stem cell mobilization factor, G-CSF, to improve the level of biomarkers of aging in patients. During treatment, an assessment of improved levels of biomarkers of aging, immunosenescence, and immune dysfunction was performed. Improvements were reported with increased levels of natural killer cell activity. Two months after treatment with G-CSF administered to the patient as in Example 18, the level of natural killer cell activity improved from 3.02 to 35.44.

While not wanting to be bound by any particular principle of action, the increase in natural killer cells results in the clinical manifestations of immune dysfunction and immunosenescence associated with chronic diseases and chronic viral infections. It has improved.

See FIGS. 26-29 for patient 9.

Diagnosis: Chronic disease, cancer (colon cancer), frailty.

According to the basic protocol outlined in Example 5, patient LK with stem cell recruitment using granulocyte colony stimulator (G-CSF) to improve the level of anti-aging biomarkers in the patient. , Infused from ABO-matched healthy allogeneic donors, treated with stem cell activation in combination with stem cell-rich plasma.

During treatment, improved levels of biomarkers of aging, immunosenescence, and early lymphoid differentiation were evaluated. Improvements by increasing naive CD4 levels and decreasing memory CD4T cells, and improved natural killer cell activity were reported. Twelve months after treatment with G-CSF administered to the patient as in Example 5, naive CD4 cell levels improved from 30.00 to 51.79.

Assessment of improvement in immune dysfunction resulted in a decrease in memory CD4T cell levels from 60.24 to 38.53.

In addition, improvement in natural killer cell activity was reported. Twelve months after treatment with G-CSF administered to the patient as in Example 5, the level of natural killer cell activity improved from 7.21 to 19.26.

In addition, improvement of B cells was reported. Twelve months after treatment with G-CSF administered to the patient as in Example 5, B cell levels improved from 36 to 46.

While not wanting to be bound by any particular principle of action, a decrease in central memory T cells and an increase in naive T cell, B cell, and natural killer cell activity results in chronic disease, cancer. Improvements in clinical manifestations of (colon cancer), frailty-related disorders of immune dysfunction, immunosenescence, and early lymphoid differentiation.

All patents and publications described herein indicate the level of one of ordinary skill in the art in which the invention is involved. All patents and publications are incorporated herein by reference to the same extent, as if each individual publication was specifically and individually incorporated as a reference.

It should be understood that although certain embodiments of the invention are illustrated, they are not limited to the particular embodiments or arrangements of the parts described and shown herein. Various modifications can be made without departing from the scope of the present invention, and it is not considered to limit the present invention to those shown and described in the specification, and the present invention is described in the specification. And it will be apparent to those skilled in the art that it is not limited to what is shown and described in any of the drawings / figures contained herein.

One of ordinary skill in the art will readily understand that the present invention is well adapted to accomplish its objectives and will readily obtain the objectives and benefits described, as well as those specific to them. The embodiments, methods, procedures and techniques described herein are current representative examples of preferred embodiments, are intended to be exemplary and not intended to limit scope. Those skilled in the art will come up with modifications and other uses of the specification, which are within the spirit of the invention and are defined by the appended claims. Although the present invention has been described in connection with certain preferred embodiments, it should be understood that the claimed invention should not be overly limited to such particular embodiments. In fact, the various modifications of the forms described to practice the present invention will be apparent to those skilled in the art and are intended to be within the claims.

Claims (17)

A method for producing a composition for improving the level of a recipient's anti-aging biomarker.
i. Granulocyte colony stimulating factor (G-CSF) is administered to the donor in an amount and duration sufficient to stimulate a significantly increased number of stem cells in the blood of a donor that is not identical to the recipient. The process of producing the composition by obtaining and retaining plasma from the donor's blood by separating the cellular material from the blood.
ii. Stem cell-rich plasma is harvested from the donor by administering an immunostimulatory effective amount of G-CSF to the donor on a first cyclic basis and obtaining plasma from the donor by separating the cell material from the blood. The process of dividing the blood into equal parts, retaining the plasma, and producing the composition, and
A method for producing a composition, which comprises any one of the processes. (A) Granulocyte colony stimulating factor (G-CSF) in an amount and duration sufficient for the donor to stimulate a significantly increased number of stem cells in the donor's plasma prior to obtaining the donor's plasma. Being a healthy young adult donor who received the
Or
(B) To determine the ABO / Rh blood group of the blood and store the aliquot for administration to a recipient whose blood group matches.
(C) Both of the above (a) and the above (b).
The method for producing a composition according to claim 1. The method for producing a composition according to claim 1 or 2, wherein the G-CSF is administered to the donor for 3 days before obtaining the plasma. Further comprising co-administering the recipient with any one or combination of G-CSF, electromagnetic signal, and umbilical cord plasma.
The method for producing a composition according to any one of claims 1 to 3, wherein the electromagnetic signal corresponds to a natural magnetic field pattern. The method for producing a composition according to any one of claims 1 to 4, further comprising a step of administering G-CSF to the donor at a dose of about 5 to about 15 μg / kg. (D) the process of freezing the aliquot of the plasma until the same ABO / Rh type recipient as the donor can receive the plasma, or (e) the process of obtaining the plasma by plasmapheresis. The method for producing a composition according to any one of claims 1 to 5, further comprising a process of performing both the above (d) and the above (e). The method for producing a composition according to claim 6, wherein the aliquot of the donor plasma is an aliquot of 50 ml. The anti-aging biomarkers include immunoaging panel, CCL 11, TGF-beta1 growth factor, nuclear factor kappa beta (NFkB), dehydroepiandrosterone sulfate (DHEA-S), plasma insulin, telomere length, cytokines, tumor necrosis. Claim 1 characterized in that it is selected from factor alpha (TNF-alpha), interleukin-10 (IL-10), natural killer cells, naive T cells, memory T cells, total B cells, or a combination thereof. The method for producing a composition according to any one of 7. The composition according to any one of claims 1 to 8, wherein the composition is for administering an aliquot of the donor's plasma to the recipient, preferably monthly. Method. The method for producing a composition according to any one of claims 1 to 9, wherein the composition is to be administered for 12 months. A composition according to any one of claims 1 to 10, wherein the composition is produced by the method. Healthy young adults pretreated with granulocyte colony stimulating factor (G-CSF) prior to obtaining said plasma from said donor in an amount and duration sufficient to significantly increase the number of stem cells in the donor's plasma. A composition consisting of plasma obtained from a donor. 12. The composition of claim 12, wherein the G-CSF is administered to the donor at a dose of 5 to 15 μg / kg, preferably for 3 days prior to obtaining the plasma. A treatment method for treating or preventing an aging-related disease, which comprises administering a therapeutically effective amount of the composition according to any one of claims 11 to 13 to a subject in need thereof.
The disease is selected from the group consisting of anemia, chronic disease, autoimmune disorder, cancer, cardiovascular disease, infectious disease, metabolic disease, neurodegenerative disease and protein energy malnutrition.
The composition is injected into an ABO / Rh blood group compatible aging recipient that requires the injection.
The composition has (i) elevated levels of naive CD4 cells, (ii) decreased levels of memory CD4 cells, (iii) elevated levels of naive CD8 cells, and (iv) levels of natural killer cells relative to the recipient. Induces changes in at least one or a combination of biomarkers, including increased levels of (v) IL10, decreased levels of (vi) TNF alpha, and (vii) increased levels of B cells.
A treatment method characterized by that. A method of treatment for improving the level of an anti-aging biomarker in said recipient, comprising administering to a recipient in need thereof a therapeutically effective amount of the composition according to any one of claims 11-13. And
The composition is injected into an ABO / Rh blood group compatible aging recipient that requires the injection.
The composition has (i) elevated levels of naive CD4 cells, (ii) decreased levels of memory CD4 cells, (iii) elevated levels of naive CD8 cells, and (iv) levels of natural killer cells relative to the recipient. Induces changes in at least one or a combination of biomarkers, including increased levels of (v) IL10, decreased levels of (vi) TNF alpha, and (vii) increased levels of B cells.
A treatment method characterized by that. The method for using the composition according to any one of claims 11 to 13 in the manufacture of a pharmaceutical product for the treatment or prevention of an aging-related disease.
The disease is selected from the group consisting of anemia, chronic disease, autoimmune disorder, cancer, cardiovascular disease, infectious disease, metabolic disease, eurodegenerative disease and protein energy malnutrition.
The composition is injected into an ABO / Rh blood group compatible aging recipient that requires injection.
The composition has (i) elevated levels of naive CD4 cells, (ii) decreased levels of memory CD4 cells, (iii) elevated levels of naive CD8 cells, and (iv) levels of natural killer cells relative to the recipient. Induces changes in at least one or a combination of biomarkers, including increased levels of (v) IL10, decreased levels of (vi) TNF alpha, and (vii) increased levels of B cells.
How to use it. The method of using the composition according to any one of claims 11 to 13 in the manufacture of a medicament for improving the level of an anti-aging biomarker in a recipient.
The composition is injected into an ABO / Rh blood group compatible aging recipient that requires injection.
The composition has (i) elevated levels of naive CD4 cells, (ii) decreased levels of memory CD4 cells, (iii) elevated levels of naive CD8 cells, and (iv) levels of natural killer cells relative to the recipient. Induces changes in at least one or a combination of biomarkers, including increased levels of (v) IL10, decreased levels of (vi) TNF alpha, and (vii) increased levels of B cells.
How to use it.

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