WO2014053105A1 - Procédé de traitement de collecte de sang de cordon ombilical, traitement et conservation de déchets de sang de cordon ombilical collecté et ses applications thérapeutiques - Google Patents

Procédé de traitement de collecte de sang de cordon ombilical, traitement et conservation de déchets de sang de cordon ombilical collecté et ses applications thérapeutiques Download PDF

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Publication number
WO2014053105A1
WO2014053105A1 PCT/CZ2013/000121 CZ2013000121W WO2014053105A1 WO 2014053105 A1 WO2014053105 A1 WO 2014053105A1 CZ 2013000121 W CZ2013000121 W CZ 2013000121W WO 2014053105 A1 WO2014053105 A1 WO 2014053105A1
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WIPO (PCT)
Prior art keywords
blood
umbilical cord
cord blood
determination
waste
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PCT/CZ2013/000121
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English (en)
Inventor
Michal VOTRUBA
Eva MATEJKOVA
Jakub SCHUREK
Lukas SCHUREK
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Primecell A.S.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Primecell A.S. filed Critical Primecell A.S.
Publication of WO2014053105A1 publication Critical patent/WO2014053105A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0665—Blood-borne mesenchymal stem cells, e.g. from umbilical cord blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48—Reproductive organs
    • A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical stem cells

Definitions

  • Cancer is in fourth place (12 %), stroke in fifth place (10 %).
  • the number of patients suffering from one or more types of cardiovascular diseases is 82.6 mil. (AHA / American Heart Association, 2012), i.e. 26 % of the population. Of that
  • the area of Advanced Therapies aims to treat acute and chronic conditions of humans or tissue replacement.
  • a major long-term scientific goal is to extend the life and function of human organs, to treat cancer and chronic or degenerative diseases.
  • the objective thus involves a gradual extension of human life utilizing cells.
  • Treatment based on one ' s own (autologous) or foreign (allogeneic) cells and supporting regeneration products in the treatment of trauma, developmental defects, cancer resections and musculoskeletal diseases is based on the availability of new functional biomaterials and their clinically relevant forms.
  • the most promising group of future biomaterials for tissue regeneration, replacement of organs are the synthetic biocompatible polymers (PLA, PGA, PEG, PHB, etc.), natural polymers (type I collagen, fibrin, chitosan, cellulose, starch, HA, etc.) and their hierarchical, functional composites with resorbable layered nanoparticles.
  • the use of synthetic polymers with the ability to manage their molecular structure and morphology of cellular carriers directly through manufacturing technology is subject to achievement of biocompatibility in clinical use, and to minimization of the impact of the products of biodegradation on the living cells (pH, C0 2> etc.).
  • Nano-fiber carriers for cell therapy started to be developed in the mid- 1990s using technique called electrospinning, and at that time nanofibers from most of the known biomaterials were successfully produced.
  • electrospinning The biggest motivation for rapid take off of this development was probably the morphological similarity of the natural extracellular matrix (ECM, Extra Cellular Matrix) and nanofiber media produced by electrospinning.
  • ECM must mimic each carrier of tissue engineering.
  • the carrier provides the cells with temporary mechanical support, it is sufficiently “chemically attractive” and its toxicity should be minimal, while it should decompose after a defined time.
  • nanofibers include wound dressing, burns, artificial skin, cartilage, bone, tendons, nerves etc.
  • the cell carriers have not just passive support role of growth vectors and mechanical protection of cells in the growth process, but their mechanical properties determine the ease of surgical handling, as well as - in conjunction with controlled adhesion of cells to the carrier - the proliferation and differentiation of the implanted cells and their morphology secreted into the ECM, and thus the entire tissue / organs.
  • TGF tumor necrosis factor
  • BMP cytokines
  • chemokines chemokines
  • Umbilical cord blood is the blood contained in the umbilical cord and placenta.
  • Umbilical cord blood is a source of various types of stem cells, in particular the hematopoietic stem cells and progenitor cells, as well as mesenchymal stem cells and other somatic stem cells.
  • Umbilical cord blood is harvested during childbirth, and further processed. It can be stored frozen for several years, and used for allogeneic and autologous transplantation.
  • the widest use is in allogeneic transplantation. They are used particularly for diseases such as congenital types of leukemia.
  • the advantage of the umbilical cord blood is the fact that it is collected at the beginning of life, when the stem cells are still unburdened by acute disease.
  • Stem cells from cord blood may also be applied in the context of regenerative medicine and cell therapy, where a number of experiments and clinical trials are ongoing.
  • Umbilical cord blood is harvested during childbirth, from umbilical cord vessels and in case of combined collection after delivery of the placenta also from the surface of placental blood vessels. Blood is placed in a sampling set and is further processed. An essential criterion for further use of allogeneic transplant is the volume of the collected blood, and the total content of the nucleated cells.
  • Adequate volume of collected blood is more than 100 ml, and the number of nucleated cells (TNC) of more than 150 x 10 7 cells, and also a sufficient amount of CD34+ cells to provide good graft survival, wherein a higher than normal amount reduces rejection by the recipient organism (GVHD, graft versus host disease).
  • TTC nucleated cells
  • Umbilical cord blood which does not meet the criteria for allogeneic transplantation or donor transplantation, is currently mostly disposed of, and thus the source of quality stem cells is wasted.
  • the present invention addresses the issue of the umbilical cord blood collections that could not be used until now - i.e. those which do not meet any of the criteria for transplant, describing the method of their further processing and production of products for clinical trials and additional patient treatment in case of certain diseases.
  • the present invention relates to a method of processing of collected samples of umbilical cord blood (UCB), wherein a) umbilical cord blood is subjected to at least one quality test ; b) umbilical cord blood that meets the criteria for at least one of the quality tests in a) is treated as an autologous or donor umbilical cord blood respectively; c) umbilical cord blood that does not meet the quality criteria of b) for autologous or donor umbilical cord blood is processed as waste blood.
  • UBC umbilical cord blood
  • the quality test as per a) is preferably selected from the group of tests determining the number of nucleated cells TNC; determination the amount of CD34+ cells; determination the volume of umbilical cord blood; determination of HLA phenotype of blood grouping and Rh factor; determination of blood cell count and vitality; serological blood tests; and blood cultures.
  • the quality test used in a) is selected from the group of: the number of nucleated cells TNC ; the amount of CD34+ cells; and determination of the volume of umbilical cord blood. Unlike the use of umbilical cord blood for transplantation, the specific further use does not need to meet all quality tests for transplantation, for example the corresponding HLA phenotype, the same blood group and Rh factor.
  • waste blood may require compliance with one or 5 more additional criteria different from the criteria, whose fulfillment leads to classification of the blood as an autologous blood, or donor umbilical cord blood.
  • Tests on the additional criteria may be performed simultaneously with the tests as per a) above, which is advantageous in terms of blood processing speed or using blood from paragraph c) falling under the category of waste blood, which is o advantageous in terms of cost savings for unused tests, or a combination of both approaches. Due to the high costs of tests this decision is very important.
  • the waste blood as per c) is further classified based on the fulfillment of the criteria of at least one quality test used in a) different from the quality tests as used in b) for autologous or donor umbilical cord blood. 5 In yet another embodiment, the waste blood from point c) is further classified in d) on the basis of meeting the criteria of at least one additional quality test different from the quality tests as per point a).
  • the quality test used in d) is selected from the group: determination of the number of nucleated cells TNC; determination of the amount of o CD34+ cells; determination of the volume of cord blood, the determination of HLA phenotype; blood-grouping and Rh factor; determination of the blood counts and vitality; serology blood tests; and blood cultures.
  • Another important embodiment of the invention relates to a method of processing of umbilical cord blood collections as described above, whereas additional fractionation 5 of waste blood is performed.
  • Fractionation is preferably carried out by methods known in the field, e.g. by various modifications of centrifugation such as gradient centrifugation and in another embodiment a corresponding method of fractionation to obtain mesenchymal stem cells is used.
  • a very important aspect of the present invention is the possibility of mixing individual samples of umbilical cord blood.
  • the condition for such successful mixing waste blood may the compliance with one or more additional criteria different from the criteria the fulfillment of which results in the classification as autologous blood or 5 donor umbilical cord blood, and may allow the use of even small amounts of cord blood unsuitable for transplant.
  • Another embodiment of a method of umbilical cord blood processing described herein thus relates to a process, which involves further mixing of waste blood or its fraction from at least two umbilical cord blood collections.
  • the waste blood or its fractions are further bound to a carrier.
  • Carriers are preferably based on nanofibers, nanocarriers, collagen carriers, hydrogels, textile meshes, tissue matrix and their combinations, particularly of nanowires mounted on a grid of biocompatible material.
  • L5 Waste blood and/or its fractions, alternatively in a form bound to a carrier, possibly mixed from several donations, obtained as described above is suitable for the manufacture of medicinal products for cardiology and neurology, in particular for the treatment of Parkinson's disease, post-traumatic and ischemic brain and spinal cord lesions, the treatment of autism and hearing loss in children.
  • Waste blood and/or its fractions, alternatively in a form bound to a carrier, possibly mixed from several collections, obtained as described above are also suitable for example as a source of induced pluripotent stem cells.
  • Waste UCB may be stored in several ways: i) individually by fractions
  • Priority areas for the use of waste blood according to the invention in the field of modern therapy are especially: a) the healing of wounds, burns, skin (including deep third degree burns with skin loss in entire thickness), replacement and augmentation of soft tissues (reconstructive and plastic surgery); treatment of musculoskeletal system; cord blood bank, b) control of diabetes and treatment of the consequences of diabetes, cardiology, stroke; c) oncology and neurology.
  • Nanocarriers, collagen carriers, hydrogels, textile gauze, tissue matrix and the combination of the above can be used as carriers for therapeutic use of the waste blood.
  • stem cells from the waste blood with carrier is particularly applied in the healing wounds and burns, to cover superficial wounds and in major surgery, cardiology and neurology.
  • neurology it is primarily used for neural damage, Parkinson's disease, brain and spinal cord lesions - traumatic and ischemic, but also in the treatment of autism and hearing loss in children.
  • Therapeutic use without the use of a carrier for example involves autoimmune diabetes (diabetes mellitus) type I and II, amyotrophic lateral sclerosis, as well as alopecia (hair loss), and psoriasis.
  • autoimmune diabetes diabetes (diabetes mellitus) type I and II
  • amyotrophic lateral sclerosis as well as alopecia (hair loss), and psoriasis.
  • Stem cells derived from waste UCB can be used in a number of supporting indications in oncology.
  • Waste UCB can be used as a source of induced pluripotent stem cells.
  • the processing of the umbilical cord blood my further involve blood fractionation using methods such as centrifugation.
  • TNC If the number of cells TNC is higher than 150 x 10 7 cells, blood is used for further processing as waste blood.
  • the collected cord blood does not have sufficient amount of CD34+ cells to ensure a good graft survival, the blood is used for further processing as waste blood.
  • volume of cord blood collected with the anticoagulant solution is 100 ml to 134 ml, this amount of suspension can be processed directly, without pre-treatment of volume. Correction of the excessive amount of blood is performed by removing excess plasma If the volume of cord blood collected with an anticoagulant solution is less than 100 ml, it is not recommended to store this blood. Such blood is used for further processing as waste blood. Separation of waste blood based on the failure to comply with other criteria
  • the blood is used for further processing as waste blood. Disposal of umbilical cord blood
  • the blood is disposed of after processing and freezing.
  • the cryoprotective solution used is DMSO with final concentration of 10%.
  • the initial material is 100% DMSO solution supplied in vials with piercing stopper with volume of 10 ml. This concentrate is used to prepare a 30% solution of DMSO in 5% albumin, and this is then mixed with freezing suspensions at the ratio of 2/3 suspension, 1/3 of DMSO (30 %), which provide a final concentration of 10% DMSO in a cryo suspension.
  • DMSO is toxic for cells and toxicity increases with increasing temperature, therefore mixing of DMSO with the cell suspension is carried out at a temperature of 0-4 ° C. Immediately after this the mixture is frozen.
  • umbilical cord blood samples were mixed: 20 ml, 33 ml, 51 ml and 89 ml, that did not meet the criterion for the volume of umbilical cord blood, but did meet the criteria of cell vitality test by trypan blue staining and were negative for antibodies for hepatitis, HIV and syphilis serology based on blood test using e.g. RR test and TPHA test.
  • Blood stem cells were isolated from the mixed blood by gradient centrifugation and the isolate was directly used for attaching to the nanofiber mesh.
  • Mesenchymal stem cells from the UCB according to the invention were used on a layer of nanofibres for dressing of superficial wounds.
  • a mesh of biocompatible material was used, with the inner space filled with a layer of nanofibres.
  • Monofilament warp knit of colorless filament was used as a matrix and spinnabie polymer based gelatin was used as a layer of biocompatible polymer nanofibres.
  • This layer contained a growth factor as the active ingredient for stimulating the cultivation, and antiseptic to prevent entry of undesirable microorganisms.
  • mesenchymal stem cells Prior to the application of mesenchymal stem cells, the medium was sterilized by gamma radiation. Mesenchymal stem cells from waste umbilical cord blood according to the invention were then placed on a sterilized nanocarrier by pipette in the form of a suspension in nutritional solution.
  • the method of processing and preservation of waste umbilical cord blood according to the solution can be used for processing and preservation of waste umbilical cord blood and for allogeneic cord blood processing and production of advanced therapies intended for clinical trials and additional patient treatment for certain diseases.
  • Priority areas of interest in the field of advanced therapies are: a) the healing of wounds, burns, skin (including deep third degree burns with full thickness skin loss), replacement and augmentation of soft tissue (reconstructive and plastic surgery) treatment of the locomotor system; cord blood bank, b) diabetes control and treatment of the consequences of diabetes, cardiology, stroke, c) oncology and neurology.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Neurology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Neurosurgery (AREA)
  • Genetics & Genomics (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Rheumatology (AREA)
  • Microbiology (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Psychology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un procédé de collecte, traitement et conservation de sang de cordon ombilical collecté et une utilisation allogénique de sang ombilical pour le traitement et la production de thérapies avancées destinées à une évaluation clinique et au traitement consécutif de patients ayant des maladies sélectionnées.˙
PCT/CZ2013/000121 2012-10-04 2013-10-04 Procédé de traitement de collecte de sang de cordon ombilical, traitement et conservation de déchets de sang de cordon ombilical collecté et ses applications thérapeutiques WO2014053105A1 (fr)

Applications Claiming Priority (2)

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CZ2012-678A CZ2012678A3 (cs) 2012-10-04 2012-10-04 Způsob zpracování odběrů pupečníkové krve, zpracování a uchování získané odpadní pupečníkové krve a její terapeutické využití
CZPV2012-678 2012-10-04

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016019332A1 (fr) * 2014-07-29 2016-02-04 Ingeneron, Inc. Procédé et appareil pour la récupération de cellules régénératives dérivées de tissu du cordon ombilical et utilisation de celles-ci
WO2020190888A1 (fr) * 2019-03-18 2020-09-24 Advanced ReGen Medical Technologies, LLC Procédés et protocoles cliniques et kits se rapportant à la fabrication et à l'utilisation de compositions thérapeutiques pour le traitement cellulaire
US11203754B2 (en) 2016-04-29 2021-12-21 Advanced ReGen Medical Technologies, LLC Microrna compositions and methods of making and using same
US11219643B2 (en) 2013-12-20 2022-01-11 Advanced ReGen Medical Technologies, LLC Compositions for cellular restoration and methods of making and using same
US11286463B2 (en) 2012-03-08 2022-03-29 Advanced ReGen Medical Technologies, LLC Reprogramming of aged adult stem cells

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
GAOXING LUO ET AL: "Promotion of cutaneous wound healing by local application of mesenchymal stem cells derived from human umbilical cord blood", WOUND REPAIR AND REGENERATION, vol. 18, no. 5, 14 September 2010 (2010-09-14), pages 506 - 513, XP055092435, ISSN: 1067-1927, DOI: 10.1111/j.1524-475X.2010.00616.x *
HIRANMOY DAS ET AL: "Ex Vivo Nanofiber Expansion and Genetic Modification of Human Cord Blood-Derived Progenitor/Stem Cells Enhances Vasculogenesis", CELL TRANSPLANTATION, vol. 18, no. 3, 1 March 2009 (2009-03-01), pages 305 - 318, XP055092536, ISSN: 0963-6897, DOI: 10.3727/096368909788534870 *
HIRANMOY DAS ET AL: "Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model", PLOS ONE, vol. 4, no. 10, 7 October 2009 (2009-10-07), pages e7325, XP055092609, DOI: 10.1371/journal.pone.0007325 *
J. C. JAIME-PEREZ ET AL: "Evaluation of Volume and Total Nucleated Cell Count as Cord Blood Selection Parameters: A Receiver Operating Characteristic Curve Modeling Approach", AMERICAN JOURNAL OF CLINICAL PATHOLOGY, vol. 136, no. 5, 26 October 2011 (2011-10-26), pages 721 - 726, XP055092383, ISSN: 0002-9173, DOI: 10.1309/AJCPFB6EXO7BJVLR *
JESSICA SUN ET AL: "Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders", TRANSFUSION, vol. 50, no. 9, 7 September 2010 (2010-09-07), pages 1980 - 1987, XP055092391, ISSN: 0041-1132, DOI: 10.1111/j.1537-2995.2010.02720.x *
JI YEON KIM ET AL: "Human Cord Blood-Derived Endothelial Progenitor Cells and Their Conditioned Media Exhibit Therapeutic Equivalence for Diabetic Wound Healing", CELL TRANSPLANTATION, vol. 19, no. 12, 1 December 2010 (2010-12-01), pages 1635 - 1644, XP055026115, ISSN: 0963-6897, DOI: 10.3727/096368910X516637 *
L. S. BARCELOS ET AL: "Human CD133+ Progenitor Cells Promote the Healing of Diabetic Ischemic Ulcers by Paracrine Stimulation of Angiogenesis and Activation of Wnt Signaling", CIRCULATION RESEARCH, vol. 104, no. 9, 8 May 2009 (2009-05-08), pages 1095 - 1102, XP055092606, ISSN: 0009-7330, DOI: 10.1161/CIRCRESAHA.108.192138 *
REEVA AGGARWAL ET AL: "Human Umbilical Cord Blood-Derived CD34+ Cells Reverse Osteoporosis in NOD/SCID Mice by Altering Osteoblastic and Osteoclastic Activities", PLOS ONE, vol. 7, no. 6, 18 June 2012 (2012-06-18), pages e39365, XP055092520, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0039365 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11286463B2 (en) 2012-03-08 2022-03-29 Advanced ReGen Medical Technologies, LLC Reprogramming of aged adult stem cells
US11219643B2 (en) 2013-12-20 2022-01-11 Advanced ReGen Medical Technologies, LLC Compositions for cellular restoration and methods of making and using same
WO2016019332A1 (fr) * 2014-07-29 2016-02-04 Ingeneron, Inc. Procédé et appareil pour la récupération de cellules régénératives dérivées de tissu du cordon ombilical et utilisation de celles-ci
US11203754B2 (en) 2016-04-29 2021-12-21 Advanced ReGen Medical Technologies, LLC Microrna compositions and methods of making and using same
WO2020190888A1 (fr) * 2019-03-18 2020-09-24 Advanced ReGen Medical Technologies, LLC Procédés et protocoles cliniques et kits se rapportant à la fabrication et à l'utilisation de compositions thérapeutiques pour le traitement cellulaire

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