WO2023190640A1 - Procédé de préparation d'une seringue pour l'administration de cellules, et procédé de transport de cellules à l'aide d'une seringue pour l'administration de cellules - Google Patents

Procédé de préparation d'une seringue pour l'administration de cellules, et procédé de transport de cellules à l'aide d'une seringue pour l'administration de cellules Download PDF

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Publication number
WO2023190640A1
WO2023190640A1 PCT/JP2023/012731 JP2023012731W WO2023190640A1 WO 2023190640 A1 WO2023190640 A1 WO 2023190640A1 JP 2023012731 W JP2023012731 W JP 2023012731W WO 2023190640 A1 WO2023190640 A1 WO 2023190640A1
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cell
syringe
cells
suspension
administration
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PCT/JP2023/012731
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English (en)
Japanese (ja)
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原田 美乃里 宮下
柚葉 市川
昌 神林
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株式会社カネカ
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    • 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
    • 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
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • 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
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/04—Preserving or maintaining viable microorganisms
    • 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

Definitions

  • the present invention relates to a method for preparing a syringe for administering cells containing a cell suspension. Furthermore, the present invention relates to a cell transport method using a syringe for cell administration.
  • cell therapy using cells is increasingly being performed in the fields of plastic surgery and orthopedics.
  • autologous cell administration using, for example, mesenchymal stem cells (MSCs) is being carried out at many medical institutions, including private clinics.
  • the cells used in such treatments are, for example, separated and cultured from tissues collected from patients, such as MSCs, prepared into a preparation with a predetermined number of cells required for treatment, and then collected. administered to the patient.
  • the cells in cell preparations are not necessarily stable and are easily affected by the environment, so cell preparations prepared by external specialized institutions may be susceptible to vibrations and other factors such as the time lapse from preparation to administration to patients and the vibrations during transportation. As a result, cell quality and viability deteriorate. It is also necessary to prevent contamination with bacteria during the preparation process and transportation of cell preparations. Therefore, it is extremely important that the prepared cells be transported to small-scale medical institutions and administered to patients while maintaining a sterile state in good condition. To this end, we minimize the quality deterioration of cell preparations prepared at external specialized institutions, prepare and transport cell preparations under conditions that do not contaminate them with bacteria, and promptly administer them to the target patient after transportation. There is a need for a means to make this possible.
  • Preparatory work for cell administration after cells arrive and are accepted at a medical institution includes, for example, thawing of cell preparations, filling of devices for cell administration, and preparation of cell concentration as necessary.
  • a cell transport method that can eliminate or minimize such preparatory work is also considered to be highly desirable for medical institutions.
  • An object of the present invention is to provide a method for preparing cell preparations containing therapeutic cells in a sterile state in a form that can be immediately administered to a subject such as a patient while minimizing preparation work even in small-scale medical institutions. That's true.
  • a further object of the present invention is to transport the prepared cell preparations from the institution that prepares the cell preparations without degrading the quality of the therapeutic cells or contaminating them with contaminants, for example, in small-scale medical facilities.
  • the purpose is to provide a method of transportation to institutions.
  • a further object of the present invention is to provide a method that makes it possible to reliably administer a cell preparation to a subject such as a patient.
  • the present inventors conducted intensive research and injected a suspension of therapeutic cells in a non-cryopreservation solution that can keep the cells stable under aseptic conditions.
  • the present inventors have developed a method for transporting the cell preparation while maintaining a high cell survival rate by sealing the prepared cell preparation, packaging it in a thermostatic container, and transporting the cell preparation.
  • the present inventors also added cell information and/or information on the subject to be administered to the cell administration syringe filled with the prepared cell preparation, thereby providing information to the subject to whom the cell preparation is to be administered.
  • a method of preparing a syringe for cell administration comprising: a filling step of filling a syringe or a syringe equipped with a suction means with the cell suspension; If necessary, a sterile tube attachment step of attaching a sterile tube to the syringe or the suction means; and a removal step of removing gas in the cell administration syringe from the cell suspension via the sterile tube. including; All the above steps are carried out under sterile conditions.
  • the above method (2) The method according to (1), wherein the filling step is performed by suctioning the cell suspension through the suction means attached to the syringe.
  • a separation step of separating the suction means and the sterilization tube from the cell administration syringe after the removal step The method according to (1) or (2), further comprising the step of attaching a sealing means for sealing the suction means attachment site of the cell administration syringe.
  • the removing step includes extruding a portion of the cell suspension from the cell administration syringe into the sterile tube.
  • the cell suspension is a suspension of cells in a non-cryopreservation solution for cell preparations.
  • the non-cryopreservation solution for cell preparations contains 0.5 to 12 (w/v)% dextran, and The method according to (5), which is a solution containing a sodium salt, a potassium salt, and a calcium salt.
  • the method according to any one of (1) to (6), wherein the cells contained in the cell suspension are mesenchymal cells.
  • the mesenchymal cells include mesenchymal stem cells.
  • a cell transport method comprising: A preparation step of preparing a syringe for cell administration filled with a cell suspension; a sealing step of sealing the cell administration syringe; a packing step of packing the sealed container produced in the sealing step into a constant temperature container together with a cold pack; and a transportation step of transporting the packed constant temperature container to a medical institution at a temperature of 0° C. to 37° C. including; A transportation method, wherein the cell administration syringe is provided with cell information and/or information on the subject to be administered. (10) The method according to (9), wherein the syringe for cell administration filled with the cell suspension is prepared by the method according to any one of (1) to (8).
  • a cell preparation can be prepared in the form of a cell administration syringe containing a suspension of therapeutic cells in a non-cryopreservation solution.
  • the cell preparation can be transported from a cell preparation preparation institution as a packaged product sealed in a sealed container and capable of maintaining a constant temperature. Furthermore, according to the method of the present invention, the prepared cell preparations and the cells that serve as their raw materials will not deteriorate in quality or be contaminated with bacteria during transportation, and will be delivered to the intended institution reliably. Can be transported.
  • the cell preparation can be reliably administered to a subject such as a patient.
  • a photograph showing an overview of the process of filling a suspension of therapeutic cells into an administration syringe is shown.
  • E This is a photograph showing the syringe with the blunt needle and sterile tube removed after the air has been removed, together with the cap that will be attached to the syringe in the next step.
  • F A photograph of a syringe with a cap attached. A photograph is shown outlining the process of transporting a syringe filled with a suspension of therapeutic cells from an institution that prepares the therapeutic cells to a medical institution that administers them.
  • A This is a photograph of a syringe with a cap attached.
  • B A photograph showing a state in which a syringe filled with a cell suspension is housed in a water absorption bag having a water absorption function.
  • C A photograph showing a water absorption bag containing a syringe housed in a barrier pouch with a sealing function.
  • D This is a photograph showing a state in which the syringe in the barrier pouch is housed in a constant temperature transport package with the syringe facing sideways.
  • E A photo showing a temperature-controlled transport package containing a barrier pouch containing a syringe, an ice pack, and cushioning material to fill the excess space, and then being packed for transport to a medical institution. It is.
  • Figure 2 shows changes in cell viability over time when syringes with different volumes are filled with different volumes of cell suspensions.
  • the relative cell viability (%) on the vertical axis indicates a relative value with the cell viability at 0 hours after the start of storage as 100%.
  • Cell survival when syringes of different capacities are filled with cell suspensions at different numbers of cells/volumes of filling liquid, and the syringes are packed in temperature-controlled transport packages (TACPack®) and transported under refrigerated conditions. shows the change in rate over time.
  • TACPack® temperature-controlled transport packages
  • FIG. 2 is a photograph showing the morphology of spheroids after spheroid suspensions of adipose-derived MSCs were filled into vials and syringes under various conditions and stored refrigerated for 24 hours under vibration conditions.
  • 2 is a photograph showing the morphology of spheroids after spheroid suspensions of human iPS cells were filled into vials and syringes under various conditions and stored refrigerated for 24 hours under vibration conditions.
  • a first aspect of the invention is a method of preparing a cell preparation for administering therapeutic cells.
  • therapeutic cells are made into a suspension under aseptic conditions, and a cell preparation is prepared as a syringe filled with the cell suspension. Since the present invention minimizes the steps up to administration at a medical institution, for example, at a medical institution administering cell preparations, a cell suspension prepared in a syringe can be immediately administered to a subject in its original form. can be administered. That is, the cell preparation prepared by the method of the present invention does not require operations such as thawing the cells or filling a device for cell administration before administering to a subject. Therefore, according to the method of the present invention, there is extremely low risk of deterioration in cell quality, contamination with bacteria, and risk of erroneous operation at the administering medical institution.
  • sterile conditions refer to conditions that can keep objects (particularly cells and the inside of containers and instruments in contact with cells) sterile for a desired period of time.
  • sterile state refers to substantially no living microorganisms (including filamentous fungi, bacteria, etc.) and viruses.
  • therapeutic cells refer to cells that are administered to a subject for the purpose of cell therapy.
  • cell suspension refers to a solution in which the above therapeutic cells are suspended in a cell preservation solution.
  • syringe refers to a device that can aspirate or inject liquids (including suspensions) or gases.
  • syringe for cell administration means a syringe containing the above cell suspension.
  • the term "suction means” refers to a means that is attached to the cell administration syringe and aspirates the cell suspension into the syringe.
  • this includes a syringe needle and a tube, but is not limited thereto, and also includes when a cell suspension is aspirated through a connector or cock.
  • the term "sterilized tube” refers to a sterilized tube that can be attached to the suction means and that can hold therein the cell suspension extruded from the cell administration syringe. means.
  • sterilized winged intravenous needles and adapter tubes are applicable, but the invention is not limited thereto, and includes anything that provides similar effects.
  • the sterilized tube can also be directly attached to the cell administration syringe to serve as the "suction means”.
  • non-cryopreservation solution for cell preparations means a solution that allows non-cryopreservation of cells. Examples include solutions containing sodium, potassium and calcium salts, and solutions containing 0.5-12 (w/v) dextran and sodium, potassium and calcium salts.
  • non-freezing storage means storage under physical conditions such as temperature and pressure that do not freeze water.
  • atmospheric pressure refers to the temperature at which water does not freeze.
  • a non-freezing temperature refers to, for example, a temperature above or above 0°C.
  • cell preparation refers to a composition containing living cells that can be applied to a subject or a raw material for therapeutic cells.
  • the term "subject” refers to an individual to whom the cell preparation of the present invention is applied.
  • a “subject” is a “patient” in need of treatment or improvement.
  • the term "patient” is defined as a person who has some kind of abnormality in their body and is not in a healthy state, such as a person suffering from some kind of disease, as well as a person who is in a healthy state but for cosmetic purposes, motor function, or physical condition. refers to a person who receives cell preparations to improve or improve their health. In this specification, this corresponds to the main subject to whom the administration syringe of the present invention is administered.
  • mesenchymal cells include all cells that constitute mesodermal tissue, and include, but are not limited to, osteoblasts, adipocytes, muscle cells, and chondrocytes. Mesenchymal cells in the present invention also include mesenchymal stromal cells and mesenchymal stem cells.
  • stem cells refer to cells that have the ability to differentiate into various cells and the ability to self-renew. Examples include somatic stem cells and pluripotent stem cells.
  • MSC Mesenchymal Stem Cell
  • the mesenchymal stem cells herein include both mesenchymal stem cells obtained from any tissue and mesenchymal stem cells prepared in vitro.
  • the standard medium is a medium obtained by adding serum, a serum replacement reagent, or a growth factor to a basal medium (eg, ⁇ MEM medium).
  • ⁇ MEM medium a basal medium obtained by adding serum, a serum replacement reagent, or a growth factor to a basal medium (eg, ⁇ MEM medium).
  • a basal medium eg, ⁇ MEM medium
  • Each step of the method for preparing a syringe for cell administration of the present invention will be explained.
  • Each step of the method of the invention is performed under sterile conditions.
  • the essential steps include a filling step, and if necessary, a sterile tube attachment step and a removal step.
  • the method for preparing a syringe for cell administration of the present invention may further include a separation step and a sealing means attachment step as optional steps.
  • a syringe or a syringe equipped with a suction means is filled with the cell suspension.
  • filling is performed by aspirating the cell suspension through a suction means attached to a syringe.
  • This step is performed under sterile conditions.
  • Aseptic conditions can be achieved by any known method, and the method used is not particularly limited. Specifically, this can be achieved, for example, by a clean bench, an isolator, a sterile workroom, a limited access barrier system, or a combination thereof. Note that in the method of the first aspect of the present invention, all other steps are performed under aseptic conditions.
  • the sterilization treatment used is not particularly limited as long as it can kill or remove microorganisms in the object to the extent that the purpose of the present invention is achieved.
  • chemical sterilization using ethanol and sodium hypochlorite heat sterilization such as high-pressure steam sterilization and dry heat sterilization, gas sterilization using ozone gas, ethylene oxide gas, plasma hydrogen peroxide gas, etc., ultraviolet rays, gamma rays, and electron beams.
  • Radiation sterilization, sterile filtration, etc. can be used.
  • Sterilization also includes, for example, sterilization.
  • Appropriate sterilization methods and conditions can generally be selected depending on the type of microorganism, the contamination situation, and the nature and condition of the object to be sterilized.
  • the syringe used in the present invention is a device that can aspirate and inject liquid or gas, and generally has a cylindrical tube on the outside and a movable pusher on the inside. has. It is sufficient that the cell suspension can be aspirated through the suction means and that it has been sterilized. Preferably, those manufactured for medical use are sterilized, and more preferably individually packaged.
  • the syringe may be made of plastic, glass, metal, etc., and any of them can be used for the purpose of the present invention.
  • the size of the syringe is not particularly limited, and is determined depending on the amount of cell suspension to be administered to the subject. For example, it is possible to use a syringe with a capacity that is 1 times or more, 2 times or more, 3 times or more, 4 times or more, 5 times or more, or 10 times or more the amount of cell suspension administered to the subject at one time. can. More specifically, syringes of 0.5 ml, 1 ml, 2 ml, 5 ml, 10 ml, 20 ml, 30 ml, 50 ml, 100 ml or larger can be used.
  • the syringe is equipped with a suction means that allows the cell suspension to be aspirated and ejected into the cell administration syringe.
  • the suction means is preferably a liquid collection needle, more preferably an injection needle such as a sharp or blunt needle, particularly preferably a blunt needle.
  • injection needles of various sizes are commercially available, any needle should be used as long as it is large enough to aspirate the cells in the cell suspension into a syringe without compromising the quality of the cells. I can do it.
  • the size of the injection needle is preferably within the range of 14 gauge (outer diameter 2.0 mm) to 30 gauge (outer diameter 0.3 mm), more preferably 18 gauge (outer diameter 1.2 mm) to 27 gauge (outer diameter 0.4 mm). However, needle sizes outside of that range can also be used.
  • the suction means must be sterile.
  • injection needles of approximately 20 to 25 gauge size are often used to aspirate cell suspensions.
  • a needle size within that range, no more than 0.09 ⁇ L of cell suspension remains in the needle.
  • an 18 gauge size needle approximately 0.5 ⁇ L of cell suspension remains in the needle.
  • FIG. 1A is a photograph of a syringe with an injection needle attached. By pulling the middle barrel of the syringe in the direction of the white arrow, the cell suspension can be aspirated into the syringe.
  • FIG. 1B is a photograph of a syringe filled with cell suspension by aspiration.
  • a tube can be attached to the tip of the syringe directly or via an adapter, and the cell suspension can be aspirated into the syringe in the same manner as with the syringe needle.
  • the cell suspension may be sucked into a syringe through a connector or cock (two-way cock, three-way cock, etc.) connected to a container such as a bag filled with the cell suspension.
  • a connector or cock two-way cock, three-way cock, etc.
  • a container such as a bag filled with the cell suspension.
  • the cells suspended in the cell suspension are, for example, therapeutic cells administered to a subject for the purpose of cell therapy. That is, a cell suspension is prepared by suspending therapeutic cells in a non-cryopreservation solution for cell preparations that is suitable for preserving the cells, particularly for preserving them in a non-frozen state. Alternatively, as will be described later, it may be a cell suspension serving as a raw material for therapeutic cells.
  • the non-cryopreservation solution for cell preparations is not particularly limited as long as it is suitable for preserving cells in a non-frozen state.
  • suitable non-cryopreservation solutions for cell preparations include solutions containing sodium, potassium and calcium salts, more preferably 0.5-12 (w/v)% dextran;
  • Examples include a solution containing a salt, more preferably a solution containing albumin in addition to the above solution.
  • the concentration of dextran contained in the non-cryopreservation solution for cell preparations is not particularly limited; w/v)%, 0.8-14(w/v)%, 0.9-13(w/v)%, or 1-12(w/v)%.
  • the concentration of albumin is not particularly limited, but examples include: 20(w/v)% or less, 15(w/v)% or less, 14(w/v)% or less, 13.5(w/v)% or less, /v)% or less, 12(w/v)% or less, 11(w/v)% or less, 10.5(w/v)% or less, 10.25(w/v)% or less, or 10.1(w/v)% or less It is.
  • the concentrations of sodium salt, potassium salt, and calcium salt are not particularly limited.
  • Another suitable non-freezing preservation solution for cell preparations is physiological saline containing albumin.
  • the albumin concentration in that case is not particularly limited, but is, for example, 0.05 to 1 (w/v)%, 0.06 to 0.5 (w/v)%, or 0.08 to 0.12 (w/v)%.
  • the method used for suspending cells in a non-cryopreservation solution is not particularly limited.
  • suspension can be achieved by aeration, refluxing the liquid, or other mechanical agitation.
  • Specific methods include, for example, methods such as pipetting and tapping.
  • the pH of the non-cryopreservation solution for cell preparations is not particularly limited as long as the cells to be preserved are viable. Specific pH is, for example, 3-9, 3.5-8.5, 4-8, 4.5-7.5, or 5-7.5.
  • the osmotic pressure of the non-cryopreservation solution for cell preparations of this embodiment is also not particularly limited as long as the cells to be preserved are viable. For example, it can be a hypotonic solution (less than 250 mOsm/L), an isotonic solution (250-380 mOsm/L), or a hypertonic solution (greater than 380 mOsm/L).
  • the type of therapeutic cells used in the method of the present invention is not particularly limited. Examples include cells derived from living tissue, cells derived from cells derived from living tissue, stem cells, cells differentiated from stem cells, or a combination thereof.
  • cells derived from living tissue include epithelial tissue-derived cells, connective tissue-derived cells, muscle tissue-derived cells, neural tissue-derived cells, or combinations thereof.
  • connective tissue-derived cells, muscle tissue-derived cells, and the like can be collectively referred to as mesenchymal cells.
  • mesenchymal cells for example, cells derived from bone marrow, adipose tissue, umbilical cord, placenta, synovium, synovial fluid, dental pulp, heart, etc. can be used.
  • Specific mesenchymal cells include, for example, skin fibroblasts, osteoblasts, tendon/ligament fibroblasts, adipocytes, chondrocytes, tendon cells, cardiomyocytes, smooth muscle cells, skeletal muscle cells, and mucin-producing cells. Examples include cells, endocrine gland-derived cells (eg, insulin-producing cells such as ⁇ -islet cells), and the like.
  • blood cells are cells differentiated from hematopoietic stem cells, unlike other mesenchymal cells, but these are also treated as mesenchymal cells.
  • dendritic cells monocytes, natural killer (NK) cells, T cells (e.g., alpha beta ( ⁇ ) T cells, gamma delta ( ⁇ ) T cells, cytotoxic T cells ( Mesenchymal cells include cytotoxic T lymphocytes (CTL), helper T cells, etc.), B cells, macrophages, neutrophils, eosinophils, etc.
  • cytotoxic T cells include cytotoxic T lymphocytes (CTL), helper T cells, etc.
  • B cells macrophages, neutrophils, eosinophils, etc.
  • these mesenchymal cells may be differentiated from, for example, pluripotent stem cells described below, and specifically may be iPS cell-derived cardiomyocytes, chondrocytes, nerve cells, etc.
  • somatic stem cells for example, somatic stem cells, pluripotent stem cells, or a combination thereof can be used.
  • somatic stem cells include mesenchymal stem cells, neural stem cells, intestinal epithelial stem cells, hair follicle stem cells, mammary gland stem cells, pigment stem cells, and the like.
  • pluripotent stem cells include embryonic stem cells (ES cells), embryonic germ cells (EG cells), germline stem cells (GS cells), and induced pluripotent stem cells. Examples include induced pluripotent stem cells (iPS cells).
  • the tissue from which the cells are derived is not particularly limited.
  • stem cells such as mesenchymal stem cells that exist in various tissues
  • cells derived from any tissue may be used, or cells derived from multiple types of tissues may be used in combination. good.
  • tissues from which mesenchymal stem cells can be derived include the tissues exemplified for mesenchymal cells.
  • mesenchymal stem cells may be derived from connective tissue or adipose tissue.
  • therapeutic cells in the present invention may be in a single cell state or in a spheroid (cell aggregate) state.
  • the subject to which the cell preparation used in the method of the present invention can be applied is not particularly limited.
  • it can be applied to biological tissues, organs, or individuals.
  • the subject of the cell preparation used in the method of the present invention may be a healthy person or may be suffering from some disease or condition.
  • Diseases and conditions include, but are not limited to, cancer, leukemia, vascular disease, stem cell exhaustion disease, bone disease, cartilage disease, ischemic disease, neurological disease, burns, chronic inflammation, ischemic cardiomyopathy, and dilation.
  • heart diseases such as type cardiomyopathy, immunodeficiency, Crohn's disease, diabetes, arthropathy, facial lipoatrophy, mastectomy, scars, age spots, wrinkles, and sagging.
  • the purpose of application is not particularly limited.
  • it can be used for purposes such as improvement, treatment and prevention of diseases and conditions, and cosmetic surgery.
  • regenerative medicine for tissue enlargement such as tissue depression
  • immunotherapy such as T cell therapy, NKT cell therapy, dendritic cell transfer therapy, gene therapy using gene-transferred cells
  • breast augmentation Examples include wrinkle removal, stain removal, anti-aging, and other cell transplant therapies.
  • the cell preparation of the present invention can be mixed with fat and used for breast reconstruction in mastectomy patients, or can be used in patients with knee osteoarthritis.
  • Application of the cell preparation used in the method of the invention allows at least some of the applied cells to function similarly to resident cells in the subject.
  • a sterile tube is attached to the suction means.
  • the sterile tube used in the present invention is a sterilized tube that can be attached to a suction means attached to a syringe for cell administration, and is a sterilized tube that can be attached to a suction means attached to a syringe for cell administration.
  • a tube is used as the suction means, it can be used as is.
  • sterile tubes examples include sterilized winged intravenous needles, adapter tubes, sterile catheters, sterile cannulas, extension tubes, drip tubes, stomach tubes, and other medical tubes, which are particularly suitable. There is a sterile winged IV needle.
  • FIG. 1C is a photograph of a winged intravenous needle commercially available from Terumo Corporation that can be used as a sterile tube.
  • the gas in the cell administration syringe is removed from the cell suspension via the sterile tube, if necessary.
  • This step is a step of extruding a portion of the cell suspension in the cell administration syringe into a sterilized tube together with the gas (for example, air) present in the cell administration syringe.
  • the gas for example, air
  • a gas such as air
  • the gas may also be administered into the blood vessel of the subject when the cell suspension is administered to the subject.
  • air enters the blood vessel of the subject, there is a risk that the air will cause occlusion of the blood vessel. Therefore, by performing this step, it is necessary to remove gas such as air from the inside of the syringe for cell administration.
  • gases such as air contained in the cell suspension are sterilized along with a portion of the cell suspension. Move into the tube.
  • this removal step can be carried out at a medical institution after transportation and before administration to the subject, it is preferable to carry out it immediately after the filling step and transport the syringe with the gas removed.
  • the outlet of the sterile tube is located away from the cell administration syringe, so that the cell administration syringe and the cell suspension extruded from the tube do not come into contact. Therefore, the cell administration syringe is not contaminated by the extruded cell suspension.
  • the method is not limited as long as it is possible to prevent the cell administration syringe from being contaminated by the extruded cell suspension, and if the syringe has a needle attached to it, the needle should be empty and sterile.
  • FIG. 1D is a photograph of the blunt needle of a syringe containing a cell suspension as one embodiment described above, with a sterile tube attached to prevent dripping.
  • gas such as air can be removed along with a portion of the cell suspension in the syringe.
  • Separation process and sealing means attachment process Considering that the cell administration syringe will be transported to a medical institution, if the cell administration syringe is attached to the suction means and sterilization tube, the cell suspension will filter out from the syringe during transportation. There is a risk of release. It is preferable in the present invention to perform a separation step of separating the suction means and the sterile tube from the cell administration syringe, and a sealing means attachment step of sealing the part of the cell administration syringe where the suction means such as the injection needle was attached. It is. Therefore, a separation step and a sealing means installation step can be performed as optional steps after performing the above-mentioned separation step.
  • FIG. 1E is a photograph showing the syringe after the separation step, with the air removed and the blunt needle and sterile tube removed, along with the cap that will be attached to the syringe in the next step.
  • a means for sealing the site is attached to the site where the suction means such as the injection needle of the administration syringe was attached.
  • the sealing means By attaching the sealing means to the cell administration syringe, the tip of the syringe to which the suction means such as the injection needle was attached is sealed. This can prevent the cell suspension from leaking from the cell administration syringe and from contaminating the cell suspension with bacteria or the like.
  • the sealing means used here is not particularly limited as long as the cell suspension can be kept in the cell administration syringe in a sterile state by sealing the tip of the syringe. Naturally, the sealing means must also be sterile.
  • sealing means examples include syringe caps, luer caps, rubber stoppers.
  • syringe caps are commercially available, and materials such as polyethylene, plastic, soft vinyl chloride, silicone rubber, etc. can be used without particular limitation.
  • a sterilized airtight seal or the like is also possible to use as a sealing means in place of a syringe cap.
  • FIG. 1F shows a photograph of a capped syringe for cell administration.
  • the second aspect of the present invention is a cell transport method.
  • a syringe for cell administration is prepared according to the first aspect, and therapeutic cells contained in the syringe for cell administration are administered to a subject, mainly a patient, at a medical institution.
  • a subject mainly a patient
  • a medical institution for example, an institution that prepares syringes for cell administration and a medical institution are different institutions. Therefore, it is necessary to maintain the prepared cells in good condition during transportation until the cell preparation is administered to a subject, and to ensure the sterility of the cell preparation during transportation.
  • a syringe for cell administration is prepared, the syringe for cell administration is sealed, the sealed container prepared in the sealing step is packed in a thermostatic container together with an ice pack, and the packed thermostatic container is Transport to a medical institution at a temperature of 0 to 37°C.
  • the constant-temperature container mentioned here may be any container that can block the influence of external temperature to some extent, and does not necessarily have to keep the temperature inside the container constant. Of course, it is more preferable that the temperature be controlled within a predetermined range. Alternatively, a package for low-temperature transportation, a cold pack, etc., which will be described later, may be used as appropriate.
  • a cell administration syringe is provided with cell information and/or information about the subject to be administered.
  • the syringe for cell administration prepared according to the first aspect is prevented from deteriorating or being contaminated with bacteria in the syringe for cell administration by a specialized organization that has prepared the syringe for cell administration. From there, the cell preparation can be transported to a medical institution where it will be administered.
  • the scale and classification of the medical institution is not limited as long as it is an institution that administers therapeutic cells to subjects.
  • it may be an advanced medical facility such as a university hospital or a general hospital, a medium-sized or small-scale medical facility, or a private clinic or orthopedic clinic.
  • an advanced medical facility such as a university hospital or a general hospital
  • a medium-sized or small-scale medical facility such as a university hospital or a general hospital
  • a private clinic or orthopedic clinic such as a private clinic or orthopedic clinic.
  • the present invention can be particularly preferably implemented because the steps up to administration can be minimized.
  • sealed container refers to a container that is sealed to prevent solid and/or gaseous foreign matter from entering the syringe for cell administration and to prevent loss of the contents filled in the syringe for cell administration. means a container capable of
  • cold pack refers to an agent that allows the "syringe for cell administration" to be kept at a low temperature, or a pouch containing the agent.
  • a “cold pack” is, for example, a composition packed in a bag containing water and a super absorbent resin (eg, sodium polyacrylate) as main components.
  • temperature-controlled transportation package refers to a transportation package that has a heat insulating property that allows the inside of the container to be maintained within a constant temperature range for a certain period of time.
  • cell information refers to information regarding the type, strain, property, origin, origin, etc. of therapeutic cells contained in a syringe for cell administration, and refers to information useful for cell identification.
  • subject information refers to information regarding the name, age, gender, disease name, etc. of the subject receiving the therapeutic cell suspension, and includes information useful for identifying the subject. means.
  • these "cell information” and “subject information” may be provided directly to the syringe for cell administration, or may be provided to a closed container that houses the syringe for cell administration.
  • the form of application is not particularly limited, and any means such as labels, stickers, printing, tags, etc. can be used.
  • these "cell information” and “subject information” may be provided in the form of symbols or barcodes. It is also possible to check the specific information corresponding to the assigned symbol or barcode via email, database, etc.
  • the method of the present invention includes a preparation step, a sealing step, a packaging step, and a transportation step as essential steps.
  • a syringe for cell administration is provided with cell information and/or subject information.
  • the cell administration syringe is sealed in a sealed container. Store it inside.
  • the sealed container used here is not particularly limited as long as it can achieve the purpose of sealing the syringe for cell administration, but examples include barrier pouches, Unipacks, Tupperware, vials, and other plastic containers with lids; Examples include glass bottles.
  • the water absorbing bag is not particularly limited as long as it has the function of absorbing leaked liquid.
  • Various products are commercially available that have a water-absorbing function by containing water-absorbing polymers, etc., and the most suitable water-absorbing bag for the cell administration syringe to be transported is selected by considering the water-absorbing function and size.
  • Examples of water-absorbing bags include "Water Catch (registered trademark)” commercially available from Sanyo Co., Ltd., “Aqua Boy (trademark)” commercially available from Akagi Co., Ltd., and water-absorbing bags commercially available from Sugiyamagen Co., Ltd.
  • Examples include “Suishokun (trademark)” which is a super absorbent polymer commercially available from Ashimori Kogyo Co., Ltd. Note that if a water absorption bag for the barrier pouch to be used is commercially available, it is preferable to use it.
  • FIG. 2A shows a photograph of a syringe with a cap.
  • FIG. 2B shows a photograph showing a state in which a syringe filled with a cell suspension is housed in a water absorption bag having a water absorption function.
  • FIG. 2C is a photograph showing a state in which a water absorption bag containing a syringe is housed in a barrier pouch having a sealing function.
  • Packaging process A sealed container such as a barrier pouch containing a syringe for cell administration is packed together with an ice pack in a package for constant temperature transport.
  • the constant-temperature transport package used in the present invention is a transport package that has heat insulation and heat retention properties that allow the inside of the container to be maintained within a certain temperature range for a certain period of time.
  • Constant temperature does not necessarily mean that the same temperature must be maintained, and temperature changes are allowed as long as it is within a set temperature range.
  • the transport package is not particularly limited, it is preferable to use a heat-insulating container containing a heat insulating material as the constant-temperature transport package.
  • packages for constant temperature transport include, but are not limited to, those containing insulation materials such as vacuum insulation materials, expanded styrene insulation materials, rigid urethane foam insulation materials, and glass wool insulation materials. .
  • Particularly suitable temperature-controlled transport packages include TACPack® commercially available from Tamai Kasei Co., Ltd., va-Q-tec® commercially available from va-Q-tec AG, and INOAC Corporation Co., Ltd.
  • Neoace registered trademark
  • the constant temperature transport package is a constant temperature transport package that can maintain the temperature inside the container at a constant temperature. As described below, the temperature during transportation is maintained between 0°C and 37°C, so when using constant-temperature transport packages, it is necessary to select a package that has a standard that allows it to be maintained at such temperatures.
  • ice packs are commercially available, such as bags containing compositions containing water and superabsorbent resins (e.g., sodium polyacrylate) as main components, but none of them can be used for the purposes of the present invention. can be used.
  • superabsorbent resins e.g., sodium polyacrylate
  • FIG. 2D is a photograph showing a state in which the syringe in the barrier pouch is housed in TACPack (registered trademark), which is a package for constant temperature transportation, with the syringe facing sideways.
  • TACPack registered trademark
  • a cushioning material into the surplus space in the constant-temperature transport package after storing the barrier pouch containing the cell administration syringe in the constant-temperature transport package. This is because it is possible to reduce the loss that cells receive due to shock during transportation.
  • Various materials can be used as the cushioning material, including air cushioning materials, foam cushioning materials, petit rolls, packing paper, and the like.
  • FIG. 2E shows a TACPack (registered trademark), which is a package for constant-temperature transport, containing a barrier pouch containing a syringe and cushioning material to fill the excess space, for transport to a medical institution. This is a photo showing the condition.
  • TACPack registered trademark
  • the temperatures during the transportation process are 0-37°C, 0-30°C, 0-25°C, 0-20°C, 0-17°C, 0-15°C, 0-14°C, 0-13°C, 0-12°C, 0 to 11°C, 0 to 10°C, 0.1 to 9°C, 0.2 to 8°C, 0.5 to 7°C, 1 to 6°C, 1.5 to 5°C, or 2 to 5°C, and cells are stable within this range. Maintain the most suitable temperature for sex. For example, it is preferable to maintain the temperature at around 4°C, which is used in the following examples.
  • the constant temperature container packed with the cell administration syringe is transported to a medical institution.
  • the cell suspension in the cell administration syringe is administered to a patient at the medical institution.
  • the present invention also provides methods of administering cell suspensions. According to the administration method of the present invention, a cell suspension can be administered while maintaining the stability of the cells.
  • the means for administering the cell suspension in the cell administration syringe to the patient is not particularly limited, but the cell administration syringe that has been transported and arrived at the medical institution may be provided with an injection needle for administration to the patient. It is convenient to connect the injection needle and administer it to the patient through the injection needle.
  • the injection needle used at this time is not particularly limited, and the thickness, length, number of needles, etc. can be arbitrarily selected depending on the disease of the patient to be administered and the purpose of administration.
  • the injection needle may not be connected directly to the syringe for cell administration, but may be connected via a tube or adapter, or may be connected to an intravenous drip line or catheter for administration.
  • the period from the end of the preparation process until the cell suspension is administered to the patient should be short, preferably within 4 days, more preferably within 3 days, even more preferably is within 2 days, most preferably within 1 day.
  • the survival rate of the cells in the cell suspension at the time of administration to the subject is 70% or more compared to the time of preparation of the cell suspension. It is. In the range of conditions examined in the following example, the cell survival rate after 96 hours was 90% or more (Example 2).
  • spheroids of pluripotent stem cells such as iPS cells produced using the suspension culture method are not administered as they are, but are differentiated and used as therapeutic cells.
  • the method of the present invention can also be employed as a means for suitably transporting spheroids of pluripotent stem cells, which are raw materials for cells for treatment.
  • Example 1 Consideration of the volume of the transport syringe and the volume of the cell suspension to be filled> (the purpose) Vials and freeze tubes are commonly used as containers for storing and transporting frozen cells. Therefore, we first conducted a preliminary test in which the prepared cell preparation was placed in a freeze tube, left standing vertically, and transported under refrigeration without freezing. As a result, it was observed that the cell survival rate tended to decrease as the concentration of cells filled in the container increased. This result suggests that when cells settle to the bottom of the tube, a large amount of cells may deplete nutrients around the cells and increase the concentration of waste products, leading to greater cell loss.
  • the present inventors came up with the idea of using a syringe as a container for cell preparations.
  • the cell concentration in the cell suspension to be filled into a syringe and the capacity of the syringe to be filled with the cell suspension will be investigated.
  • Method 1 Preparation of cell suspension After thawing and washing the aspirated fat-derived MSCs that had been stored frozen, the amount of cells was reduced to 1 ⁇ 10 8 cells by replacing the washing solution with a non-cryopreservation solution for cell preparations and suspending them. Cell suspensions of the following levels were prepared in the following manner. The composition of the non-cryopreservation solution for cell preparations used in this example is as shown below.
  • Lactated Ringer's solution (Lactec Injection, Otsuka Pharmaceutical Factory (for composition etc., see the December 2016 revised (9th edition) package insert)) + dextran 4(w/v)% + human serum albumin (HSA) 5(w/v) )%
  • the prepared cell suspension was filled into a syringe or flow tube with the following volume.
  • a syringe as shown in Figure 1, after aspirating the cell suspension through a blunt needle, attach a sterile tube to remove the gas inside the syringe, and then separate the blunt needle and sterile tube. , the cap was attached.
  • the total cell concentration in this measurement is calculated by mixing equal amounts of cell suspension, cell processing reagent A100 (model number: 910-0003), and cell processing reagent B (model number: 910-0002).
  • the PI solution was used as a staining target, aspirated into the above-mentioned cassette, and measured.
  • the cell number and survival rate of the obtained adipose-derived MSCs were calculated from the cell concentration measurement values. The calculation formula was as follows.
  • Viability rate of adipose-derived MSC 100 - (dead cell concentration (cells/mL) / (total cell concentration (cells/mL) x 3 (dilution factor during measurement)) x 100) Note that the cell viability data was standardized with the value after 0 hours as 100%.
  • FIG. 3 shows the results of measuring changes in cell viability in the cell suspension at each level.
  • the cell viability of level (1) in which the cell suspension was filled in a syringe, gradually decreased over time, but even after 96 hours, it was still 90% lower than at the start of storage. % cell viability was maintained.
  • Level (2) and Level (3) in which the cell suspension was filled in the syringe also maintained a cell survival rate of 90% after 72 hours compared to the time at the start of storage. Therefore, it has been found that filling and storing the cell suspension in a syringe is suitable from the viewpoint of cell survival rate.
  • level (4) in which the cell suspension was filled in a flow tube also maintained a cell viability of 90% compared to the time at the start of storage even after 72 hours.
  • level (5) which is a test in which a cell suspension was actually transported using a flow tube (corresponding to the preliminary test of the reference example), the cell The survival rate had fallen to 69% at the start of preservation.
  • a syringe would be suitable as a container for filling the cell suspension. Furthermore, it was predicted that the decrease in cell survival rate during refrigerated transportation could be suppressed by lowering the cell concentration and storing the cell administration syringe horizontally to increase the area on which cells settle.
  • Example 2 Changes over time in cell viability when cell products filled with cell suspensions in syringes are transported under refrigerated conditions under various conditions> (the purpose)
  • the size of the syringe which is a candidate container for containing the product cells, and the capacity of the suspension to be filled in it.
  • a transport test is conducted using a syringe as a container, and the cell survival rate during transport is evaluated over time.
  • Method 1 Preparation of cell suspension and filling of the cell suspension into a syringe After thawing and washing the aspirated fat-derived MSCs that had been stored frozen, the washing solution was used as a non-cryopreservation solution for cell preparations (lactated Ringer's solution + dextran 4 (w/ A cell suspension was prepared by substituting the cell suspension with HSA 1.5 (w/v)%). The prepared cell suspension was filled into a syringe in the same manner as in Example 1.
  • the size of the syringe filled with the cell suspension, the number of filled cells/amount of cell suspension, and whether or not to be transported are as follows.
  • FIG. 4 shows the results of measuring changes in cell viability in the cell suspension at each level. As shown in FIG. 4, at all levels, although the survival rate tended to decrease over time, the survival rate of 90% or more at the start of storage was maintained even after 96 hours.
  • the survival rate was maintained higher at level (3), where the number of cells was smaller (lower cell concentration).
  • Level (1) in which a 10 mL syringe was filled with a suspension of 10 ⁇ 10 7 cells/5 mL Level (4) in which a 10 mL syringe was filled with a suspension of 10 ⁇ 10 7 cells/10 mL, and 10 ⁇ 10 7 cells
  • Level (5) in which a 2.5 mL syringe was filled with 2.5 mL of suspension there was no significant difference in survival rate after 72 hours.
  • Example 3 Changes in cell recovery rate over time when cell products filled with cell suspensions in syringes are transported under refrigerated conditions under various conditions> (the purpose)
  • the size of the syringe which is a candidate container for containing the product cells, and the capacity of the suspension to be filled into it.
  • a transport test is conducted using a syringe as a container, and the cell recovery rate during transport is evaluated over time.
  • the size of the syringe filled with the cell suspension, the number of filled cells/amount of cell suspension, and whether or not to be transported are as follows.
  • FIG. 5 shows the results of measuring changes in cell recovery rate in the cell suspension at each level. As shown in Figure 5, the average values of cell recovery rates were approximately 98, 96, 92, 92, 91 (%). Therefore, the cell recovery rate was over 90% at all levels. Therefore, when a syringe was used as a container for refrigerated transportation of product cells, the cell loss was less than 10%, which was a very good result.
  • Example 4 Confirming the sterility of the product after filling it into a syringe and transporting it under refrigeration>
  • a culture medium filling test (process simulation) was conducted to verify that sterility was maintained during the process of filling refrigerated transport cells into syringes and transporting them with TACPack (registered trademark).
  • TACPack registered trademark
  • Syringes 15 syringes: 10 mL syringes x 5, 5 mL syringes x 5, 2.5 mL syringes x 5) filled with culture medium were prepared in the same manner as in Example 1, except that the culture medium was used instead of the cell suspension. After being transported from Yokohama to Kobe, the syringes were cultured for 14 days and it was confirmed that there was no bacterial growth in all 15 syringes. This confirmed that sterility could be ensured in the cell filling process and refrigerated transport process in the present invention.
  • Example 5 Simulation experiment of refrigerated transport of fat-derived MSC spheroids> 1. Preparation of spheroid suspension After thawing human adipose-derived MSCs that had been stored frozen, MEM ⁇ was added with 5% hPL, 0.1% gentamicin (Takada Pharmaceutical), and 0.1% 0.25 mg/mL amphotericin B (Bristol-Myers). (Life Technologies Japan) was used as a medium, and adhesive culture was performed at a seeding density of 1 ⁇ 10 5 cells/cm 2 at 37° C. in a 5% CO 2 atmosphere. On the third day of culture, cells were detached, washed, and collected as single cells.
  • EZSPHERE registered trademark
  • SP Microplate 6well APC Techno Glass
  • the culture solution volume is 3 mL
  • the cell density at the start of culture is 2.7 ⁇
  • the collected cells were seeded at 10 6 cells/well and cultured in suspension at 37° C. in a 5% CO 2 atmosphere. Three days later, the medium was separated by centrifugation and spheroids were collected.
  • spheroids After washing the spheroids, suspend them in a non-cryopreservation solution for cell preparations (Lactated Ringer's solution + Dextran 4 (w/v)% + HSA 1.5 (w/v)%) to a concentration of 1 ⁇ 10 6 cells/mL. A suspension was prepared. The number of cells was determined based on the results obtained by converting spheroids sampled at the end of culture into single cells by pipetting with TrypLE (trademark) Select (Life Technologies Japan Co., Ltd.) and measuring them using NucleoCounter NC-200.
  • TrypLE trademark
  • the upper photograph in Figure 6 shows the state of spheroids in the suspension at the start of storage
  • the lower four photographs in Figure 6 indicates the state of spheroids in suspension after storage.
  • most of the spheroids collapsed in the suspension filled in the vial levels (3) and (4)
  • many single cells were observed instead, indicating that the spheroid shape could not be maintained during transportation.
  • StemFit (registered trademark) AK02N (Ajinomoto Co., Ltd.) was used as the medium, and the day on which the cells were seeded was the 0th day of culture, and the entire amount of the medium was replaced on the 1st, 4th, and 6th day of culture.
  • the amount of medium was 60 mL/dish only when changing the medium on the first day of culture, and 30 mL/dish at other times.
  • Y-27632 (Fuji Film Wako Pure Chemical Industries, Ltd.) was added to the medium at a final concentration of 10 ⁇ M.
  • the culture medium for seeding was StemFit (registered trademark) AK02N (Ajinomoto Co.) supplemented with Y-27632 at a final concentration of 10 ⁇ M and IWR-1 endo at a final concentration of 20 ⁇ M.
  • the culture temperature was 37°C and the amount of gas supplied was was maintained at 0.1 L/min, carbon dioxide gas supply was automatically controlled to maintain pH between 7.1 and 7.2, and the stirring speed was 60 mm/sec.
  • the day the culture was started was set as the 0th day of culture, and the entire amount of the medium was replaced on the 1st day and the 2nd day of culture.
  • Spheroids were suspended in Ringer's solution (Otsuka Pharmaceutical Co., Ltd.) containing Y-27632 at a final concentration of 10 ⁇ M at a concentration of 1 ⁇ 10 7 cells/mL to prepare a spheroid suspension.
  • the number of cells was determined based on the results obtained by converting spheroids sampled at the end of culture into single cells by pipetting with Accutase (Innovative Cell Technology) and measuring them using NucleoCounter NC-200.
  • the present invention it has become possible to prepare a syringe for cell administration containing a suspension of therapeutic cells without contamination with unintended bacteria or contaminants. Furthermore, the cell administration syringe containing the cell suspension is transferred from the institution that prepares it to the medical institution that administers the therapeutic cells to the subject without deteriorating the quality of the cells and maintaining sterility. It became possible to transport. In addition, the present inventors have found that by adding cell information and/or information on the subject to be administered to the cell administration syringe, it becomes possible to reliably administer therapeutic cells to the subject to be administered. Developed a transportation method. The present invention greatly contributes to the implementation of cell therapy, especially in small-scale medical institutions. All publications, patents, and patent applications cited herein are incorporated by reference in their entirety.

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Abstract

La présente invention a pour but de procurer un procédé de préparation d'une préparation cellulaire contenant des cellules thérapeutiques à l'état aseptique dans une forme posologique pouvant être administrée à un sujet immédiatement sans qu'il soit nécessaire d'effectuer un travail préliminaire dans un établissement médical. Un autre but de la présente invention est de procurer un procédé de transport d'une préparation cellulaire d'une installation de préparation de la préparation cellulaire vers une installation médicale selon la détérioration de la qualité des cellules thérapeutiques ou la contamination par des germes.　La présente invention concerne : un procédé pour préparer une préparation cellulaire en remplissant une suspension dans une seringue pour injection à l'état aseptique, la suspension comprenant des cellules thérapeutiques en suspension dans une solution non cryoconservée capable de conserver les cellules de manière stable ; et un procédé pour transporter la préparation cellulaire préparée tout en conservant un taux de survie cellulaire élevé et un état aseptique, le procédé comprenant le scellement hermétique de la préparation cellulaire, le conditionnement de la préparation cellulaire scellée dans un conteneur à température constante, puis le transport de la préparation cellulaire conditionnée.
PCT/JP2023/012731 2022-03-30 2023-03-29 Procédé de préparation d'une seringue pour l'administration de cellules, et procédé de transport de cellules à l'aide d'une seringue pour l'administration de cellules WO2023190640A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011067588A (ja) * 2009-09-22 2011-04-07 Olympus Corp 細胞注入デバイス
JP2014513918A (ja) * 2011-02-18 2014-06-19 ステムサイト インコーポレーテッド 幹細胞の包装および輸送
JP2014517830A (ja) * 2011-05-03 2014-07-24 イミュノバティブ セラピーズ，リミテッド 生細胞を含む生物学的薬剤の取り扱い方法
CN204688616U (zh) * 2015-06-19 2015-10-07 黑龙江天晴干细胞股份有限公司 一种用于细胞制剂注射和回输用的套装盒
WO2020231968A1 (fr) * 2019-05-15 2020-11-19 Stemcyte Inc. Conditionnement et expédition de cellules à une concentration élevée
CN113549536A (zh) * 2021-07-13 2021-10-26 深圳赛桥生物创新技术有限公司 一种基于全封闭式注射器的无菌细胞取样装置及方法
CN215045037U (zh) * 2021-06-29 2021-12-07 成都云测医学生物技术有限公司 一种便于储存和运输膝关节干细胞注射液的包装盒

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011067588A (ja) * 2009-09-22 2011-04-07 Olympus Corp 細胞注入デバイス
JP2014513918A (ja) * 2011-02-18 2014-06-19 ステムサイト インコーポレーテッド 幹細胞の包装および輸送
JP2014517830A (ja) * 2011-05-03 2014-07-24 イミュノバティブ セラピーズ，リミテッド 生細胞を含む生物学的薬剤の取り扱い方法
CN204688616U (zh) * 2015-06-19 2015-10-07 黑龙江天晴干细胞股份有限公司 一种用于细胞制剂注射和回输用的套装盒
WO2020231968A1 (fr) * 2019-05-15 2020-11-19 Stemcyte Inc. Conditionnement et expédition de cellules à une concentration élevée
CN215045037U (zh) * 2021-06-29 2021-12-07 成都云测医学生物技术有限公司 一种便于储存和运输膝关节干细胞注射液的包装盒
CN113549536A (zh) * 2021-07-13 2021-10-26 深圳赛桥生物创新技术有限公司 一种基于全封闭式注射器的无菌细胞取样装置及方法

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