WO2021210515A1 - 腎臓中のｃｄ２５陽性の制御性ｔ細胞増加剤 - Google Patents

腎臓中のｃｄ２５陽性の制御性ｔ細胞増加剤 Download PDF

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WO2021210515A1
WO2021210515A1 PCT/JP2021/015093 JP2021015093W WO2021210515A1 WO 2021210515 A1 WO2021210515 A1 WO 2021210515A1 JP 2021015093 W JP2021015093 W JP 2021015093W WO 2021210515 A1 WO2021210515 A1 WO 2021210515A1
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cells
mesenchymal stem
cell
stem cells
regulatory
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French (fr)
Japanese (ja)
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彰一 丸山
和拡 古橋
田中　章仁
宗稔 唐澤
幸成 高尾
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Rohto Pharmaceutical Co Ltd
Tokai National Higher Education and Research System NUC
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Rohto Pharmaceutical Co Ltd
Tokai National Higher Education and Research System NUC
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Priority to EP21788756.1A priority Critical patent/EP4137141A4/en
Priority to CN202180021798.6A priority patent/CN115297877A/zh
Priority to JP2022515358A priority patent/JPWO2021210515A1/ja
Priority to US17/918,390 priority patent/US20230158076A1/en
Publication of WO2021210515A1 publication Critical patent/WO2021210515A1/ja
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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
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C12N5/0637—Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
    • 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
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/50—Cell markers; Cell surface determinants
    • C12N2501/599—Cell markers; Cell surface determinants with CD designations not provided for elsewhere

Definitions

  • the present invention relates to a CD25-positive regulatory T cell enhancer in the kidney.
  • IgA nephropathy is a chronic primary glomerulonephritis in which deposits mainly composed of IgA are found in the mesangial region of the glomerulus. It is suspected that some antigen stimulates the production of IgA antibody, and the immune complex (IC) in which the antigen and antibody are bound deposits in the glomerulus, causing glomerulonephritis. Since no radical cure has been obtained for the treatment of this disease, symptomatic treatments such as renin angiotensin system inhibitors, corticosteroids (pulse therapy), immunosuppressants, and tonsillectomy have been performed. Therefore, the development of a treatment method is desired.
  • Mesenchymal stem cells are pluripotent cells isolated from bone marrow for the first time by Friedenstein (see Non-Patent Document 1). Mesenchymal stem cells are attracting attention as a promising cell source in cell therapy because they have the ability to differentiate into bone, cartilage and fat. Recently, it is known that there are cells having the same function as stromal cells of fetal appendages such as adipose tissue, placenta, umbilical cord, and fetal membrane. Therefore, mesenchymal stem cells may be referred to as stromal cells (Mesenchymal Stromal Cell).
  • mesenchymal stem cells used for disease treatment include acute graft-versus-host disease (GVHD) treatment in hematopoietic stem cell transplantation (see Non-Patent Document 2), Crohn's disease treatment for inflammatory bowel disease, and cerebral infarction treatment (non-patent). (See Patent Document 3).
  • GVHD graft-versus-host disease
  • Non-Patent Document 2 Crohn's disease treatment for inflammatory bowel disease
  • cerebral infarction treatment non-patent.
  • An object of the present invention is to provide a fundamental therapeutic method for renal diseases such as glomerulonephritis such as IgA nephropathy under the above-mentioned circumstances.
  • the invention made to solve the above problems relates to a CD25-positive regulatory T cell increasing agent in the kidney.
  • a CD25-positive regulatory T cell increasing agent in the kidney containing mesenchymal stem cells [2] The CD25-positive regulatory T cell-increasing agent in the kidney according to [1], which further contains a cryopreservation solution having a concentration of less than 5% (v / v). [3] The CD25-positive regulatory T cell increasing agent in the kidney according to [2], wherein the cryopreservation solution is a cryopreservation solution containing DMSO (Dimethyl sulfoxide). [4] The CD25-positive regulatory T cell increasing agent in the kidney according to any one of [1] to [3], which is used for treating renal diseases.
  • a method for treating renal disease which comprises increasing CD25-positive regulatory T cells in the kidney by administration of a CD25-positive regulatory T cell-increasing agent.
  • the method for treating renal disease according to [7], wherein the CD25-positive regulatory T cell increasing agent contains mesenchymal stem cells.
  • CD25-positive regulatory T cells in the kidney can be increased, so that the function, structure, etc. of the diseased part such as the kidney can be remarkably improved.
  • renal diseases such as glomerulonephritis such as IgA nephropathy.
  • the mesenchymal stem cells contained in the regulatory T cell increasing agent of the present invention are unlikely to cause rejection even to allogeneic subjects, the donor cells prepared in advance are expanded and cryopreserved. Can be used. Therefore, there is an advantage that it is easy to commercialize and a stable and constant effect can be easily obtained as compared with the case where self-mesenchymal stem cells are prepared and used.
  • the measurement results of serum creatinine concentration (left figure), blood urea nitrogen (center figure) and crescent score (right figure) of nephritis-onset rats 3 days after the final administration of mesenchymal stem cells of anti-GBM nephritis rats are shown.
  • the measurement results of serum creatinine concentration (left figure) and blood urea nitrogen (right figure) of anti-GBM nephritis rats 3 days after the final administration of mesenchymal stem cells are shown.
  • the measurement results of serum creatinine concentration (left figure) and blood urea nitrogen (right figure) of anti-GBM nephritis rats 3 days after the final administration of mesenchymal stem cells are shown.
  • the measurement results of serum creatinine concentration (left figure) and blood urea nitrogen (right figure) of anti-GBM nephritis rats 3 days after the final administration of mesenchymal stem cells are shown.
  • the ratio of CD25-positive Treg cells among CD45-positive cells in the kidney of anti-GBM nephritis rats 3 days after the final administration of mesenchymal stem cells is shown.
  • the results of comparison between the proportion of CD25-positive Treg cells in the kidneys of anti-GBM nephritis rats 3 days after the final administration of mesenchymal stem cells and the serum creatinine concentration are shown.
  • the regulatory T cell increasing agent of the present invention is characterized by containing mesenchymal stem cells.
  • T cells are cells that have a protein called a T cell receptor on the cell surface and specifically recognize and activate foreign substances through this receptor. From its function, T cells become helper T cells that activate their functions by acting on other immune cells such as killer T cells, B cells and macrophages (phagocytic cells) that specifically kill virus-infected cells and cancer cells. It is roughly classified. Regulatory T cells (Treg cells) are one of the T cells, and are cells having a function of acting on immune cells such as killer T cells, helper T cells, B cells, and macrophages to suppress their activation. Regulatory T cells have the function of suppressing the immune response, and suppress the excessive immune response that causes autoimmune diseases, inflammatory diseases, allergic diseases, and the like. In the present invention, the surface antigen expression, CD45 + CD3 + CD4 + CD8 - have determined that CD25 + Foxp3 + a is T cell regulatory T cells (Treg cells).
  • the mesenchymal stem cell is a cell that has the ability to differentiate into cells belonging to the mesenchymal system (osteocytes, myocardial cells, chondrocytes, tendon cells, adipocytes, etc.) and can proliferate while maintaining the ability. Means.
  • mesenchymal stem cell used in the present invention means the same cell as a stromal cell, and does not particularly distinguish between the two.
  • tissue containing mesenchymal stem cells examples include adipose tissue, umbilical cord, bone marrow, umbilical cord blood, endometrial membrane, placenta, dermis, skeletal muscle, bone membrane, tooth sac, periodontal ligament, pulp, tooth germ and the like. .. Therefore, for example, adipose tissue-derived mesenchymal stem cells mean mesenchymal stem cells contained in adipose tissue, and may be referred to as adipose tissue-derived stromal cells.
  • adipose tissue-derived mesenchymal stem cells adipose tissue-derived mesenchymal stem cells, umbilical band-derived mesenchymal stem cells, bone marrow-derived mesenchymal stem cells, placen-derived mesenchymal stem cells, and dental pulp-derived mesenchymal stem cells are preferable, and adipose tissue-derived mesenchymal stem cells, Bone cell-derived mesenchymal stem cells and umbilical band-derived mesenchymal stem cells are more preferable, adipose tissue-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells are even more preferable, and adipose tissue-derived mesenchymal stem cells are particularly preferable.
  • the mesenchymal stem cells in the present invention are preferably allogeneic or allogeneic to the subject. Since mesenchymal stem cells are less likely to cause rejection of allogeneic subjects, pre-prepared donor cells are expanded and cryopreserved, and the mesenchymal stem cells in the therapeutic agent of the present invention are used. Can be used as. Therefore, the mesenchymal stem cells in the present invention can be easily commercialized and can obtain a stable and constant effect as compared with the case where self-mesenchymal stem cells are prepared and used. It is more preferable that they are allogeneic.
  • the mesenchymal stem cells in the present invention are, for example, growth characteristics (eg, population doubling ability from passage to aging, doubling time), nuclear type analysis (eg, normal nuclear type, maternal lineage or neonatal lineage), flow cytometry.
  • Surface marker expression by metric eg, FACS analysis
  • immunohistochemistry and / or immunocytochemistry eg, epitope detection
  • gene expression profiling eg, gene chip array; reverse transcription PCR, real-time PCR, conventional PCR, etc. Polymerase chain reaction
  • miRNA expression profiling eg, protein array, protein secretion of cytokines (eg, plasma coagulation analysis, ELISA, cytokine array), metabolites (metabolome analysis), other methods known in the art, etc. It may be characterized.
  • the mesenchymal stem cells can be prepared by a method well known to those skilled in the art.
  • adipose tissue-derived mesenchymal stem cells can be obtained, for example, by the production method described in US Pat. No. 6,777,231.
  • the mesenchymal stem cells in the present invention may be cells that have been cryopreserved and thawed as appropriate as long as they have a CD25-positive regulatory T cell increasing effect and a disease therapeutic effect.
  • cryopreservation can be performed by suspending mesenchymal stem cells in a cryopreservation solution well known to those skilled in the art and cooling the cells.
  • Suspension can be performed by exfoliating the cells with a release agent such as trypsin, transferring them to a cryopreservation container, treating them as appropriate, and then adding a cryopreservation solution.
  • cryopreservation solution examples include DMSO (Dimethyl sulfoxide) as a cryoprotectant.
  • DMSO Dimethyl sulfoxide
  • cryopreservation liquids for example, cryopreservation provided by Bioverde, Japan Genetics Co., Ltd., Reprocell, Xenoac, Cosmo Bio, Kojin Bio Co., Ltd., Thermo Fisher Scientific Co., Ltd., etc. A liquid may be used.
  • the mesenchymal stem cells in the cryopreserved state can be thawed immediately before use, suspended in the cryopreserved solution, and directly mixed with a solution such as an infusion solution or a medium to be used as a regulatory T cell increasing agent. It is also possible to remove the cryopreservation solution by a method such as centrifugation and then suspend it in a solution such as an infusion solution or a medium to use it as a regulatory T cell increasing agent.
  • the concentration of the cryopreservation solution in the regulatory T cell enhancer is less than 5% (v / v), preferably less than 2% (v / v), more preferably 1.65% (v / v) or less. ..
  • the "infusion solution” in the present invention refers to a solution used in the treatment of humans, and is not particularly limited, but for example, physiological saline solution, Japanese Pharmacopoeia physiological saline solution, 5% glucose solution, Japanese Pharmacopoeia. Glucose injection solution, Ringer's solution, Japanese Pharmacopoeia Ringer's solution, Lactobacillus Ringer's solution, Ringer's acetate solution, No. 1 solution (starting solution), No. 2 solution (dehydration supplement solution), No. 3 solution (maintenance solution), No. 4 solution (postoperative recovery solution) And so on.
  • Thawing of cryopreserved cells can be performed by a method well known to those skilled in the art. For example, a method performed by standing or shaking in a constant temperature bath at 37 ° C. or in a hot water bath is exemplified.
  • the regulatory T cell increasing agent of the present invention may contain a pharmaceutically acceptable carrier or additive according to a conventional method, as long as the effect of the present invention is not impaired. good.
  • the controllable T cell increasing agent of the present invention is physiological saline, Japanese Pharmacopoeia physiological saline, 5% glucose solution, Japanese Pharmacopoeia glucose injection, Ringer's solution, Japanese Pharmacopoeia Ringer's solution, Lactobacillus Ringer's solution, Ringer's acetate solution, Ringer's bicarbonate solution No. 1.
  • Suspension using infusion solution such as solution (starting solution), solution 2 (dehydration supplement solution), solution 3 (maintenance solution), solution 4 (postoperative recovery solution), or cell culture medium such as DMEM. Alternatively, it can be diluted and used.
  • the controllable T cell increasing agent of the present invention can be suitably used for the treatment of renal diseases (for the treatment of renal diseases), and among them, acute glomerulonephritis, glomerulonephritis such as chronic glomerulonephritis, and interstitial. It can be suitably used for the treatment of nephritis, acute nephritis syndrome, recurrent, persistent hematology, chronic nephritis syndrome, nephrotic syndrome, IgA nephritis, lupus nephritis or acute progressive nephritis syndrome.
  • the content of mesenchymal stem cells in the regulatory T cell increasing agent of the present invention is adjusted according to the patient's condition (body weight, age, symptoms, physical condition, etc.), the dosage form of the regulatory T cell increasing agent of the present invention, and the like.
  • the number of cells is 1 ⁇ 10 3 to 1 ⁇ 10 12 cells / time, preferably 1 ⁇ 10 4 to 1 ⁇ 10 11 cells / time, more preferably 1 ⁇ .
  • the dose per patient's body weight is 1 ⁇ 10 to 5 ⁇ 10 10 pieces / kg, preferably 1 ⁇ 10 2 to 5 ⁇ 10 9 pieces / kg, and more preferably 1 ⁇ 10 3 to 5 ⁇ 10. 8 pieces / kg, more preferably 1 ⁇ 10 4 to 5 ⁇ 10 7 pieces / kg.
  • this dose may be administered as a single dose in a plurality of times, or this dose may be administered in a plurality of times.
  • the regulatory T cell increasing agent of the present invention may be administered together with one or more other agents.
  • Other agents include any agent that can be used as a therapeutic agent for the kidneys, such as immunosuppressive agents such as corticosteroids, misolibin, cyclosporin, tachlorimus, cyclophosphamide, dipyridamol, dilazep hydrochloride hydrate.
  • Antiplatelet drugs such as heparin, anticoagulants such as Walfarin potassium, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), antihypertensive drugs such as calcium antagonists, loop diuretics such as frosemide and azosemide. Examples include drugs, concentrated albumin preparations, and antihypertensive drugs.
  • the present invention also includes a method of increasing CD25-positive regulatory T cells in the kidney, which comprises administering mesenchymal stem cells. This method can also be rephrased as a method for increasing CD25-positive regulatory T cells in the kidney, which comprises administering the above-mentioned regulatory T cell increasing agent.
  • mesenchymal stem cells, CD25-positive regulatory T cells, and regulatory T cell increasing agents the explanation in the section of regulatory T cell increasing agents can be applied.
  • the present invention includes a method for treating renal disease, which comprises increasing CD25-positive regulatory T cells in the kidney by administration of a CD25-positive regulatory T cell-enhancing agent.
  • the CD25-positive regulatory T cell increasing agent preferably contains mesenchymal stem cells.
  • mesenchymal stem cells, CD25-positive regulatory T cells, and regulatory T cell increasing agents the explanation in the section of regulatory T cell increasing agents can be applied.
  • renal diseases acute glomerulonephritis, glomerulonephritis such as chronic glomerulonephritis, interstitial nephritis, acute nephritis syndrome, recurrent, persistent hematology, chronic nephritis syndrome, nephrotic syndrome, IgA nephropathy, Lupus nephritis or acute progressive nephritis syndrome can be mentioned, and the treatment method of the present invention is effective for glomerulonephritis such as acute glomerulonephritis and chronic glomerulonephritis among these diseases.
  • Anti-GBM mouse IgG (TF78) that specifically binds to ⁇ 4 (IV) NC1 of rat glomerular basement membrane (GBM) is administered to rats (WKY / NCrj, female) for anti-glomerular basement membrane nephritis. (Goodpasture syndrome, anti-GBM nephritis) developed.
  • the cells were suspended in 2 mL of HBSS and used for administration, and only HBSS was administered to the target group (Control group).
  • Serum creatinine concentration (S-Cr), blood urea nitrogen (S-BUN) and crescent scores were measured on day 7.
  • Administration of bone marrow-derived MSC and fat-derived MSC suppressed the increase in creatinine concentration, blood urea nitrogen, and crescent score due to anti-GBM nephritis, but it was particularly significantly suppressed by administration of fat-derived MSC (Fig. 1).
  • mice Similar to Example 1, rats (WKY / NCrj, female) developed anti-GBM nephritis. Immediately after administration of anti-GBM mouse IgG, 2 ⁇ 10 6 cells of bone marrow-derived mesenchymal stem cells (bone marrow-derived MSC group) or adipose-derived mesenchymal stem cells (fat-derived MSC) were administered on the 2nd and 4th days. .. The cells were suspended in 2 mL of the starting solution (manufactured by Otsuka Pharmaceutical Factory) and 5% (v / v) cryopreservation solution (STEM-CELLBANKER® GMP Grade, containing 10% DMSO) and used for administration.
  • the starting solution manufactured by Otsuka Pharmaceutical Factory
  • 5% (v / v) cryopreservation solution STEM-CELLBANKER® GMP Grade, containing 10% DMSO
  • Serum creatinine concentration (S-Cr) and blood urea nitrogen (S-BUN) were measured on the 7th day. Increased creatinine concentration, increased blood urea nitrogen, and increased crescent score due to anti-GBM nephritis were not suppressed by administration of bone marrow-derived or fat-derived MSC and 5% (v / v) cryopreservation solution (Fig. 2).
  • mice Similar to Example 1, rats (WKY / NCrj, female) developed anti-GBM nephritis. Immediately after administration of anti-GBM mouse IgG, 2 ⁇ 10 6 cells of adipose-derived mesenchymal stem cells (fat-derived MSC group), 2 ⁇ 10 6 cells of adipose-derived mesenchymal stem cells and 5% on days 2 and 4. (V / v) concentration cryopreservation solution (STEM-CELLBANKER® GMP Grade, 10% DMSO containing, fat-derived MSC + S group), 5% (v / v) concentration cryopreservation solution (Control + S group) was administered. bottom.
  • the cells and cryopreservation solution were suspended in 2 mL of the starting solution (manufactured by Otsuka Pharmaceutical Factory) and used for administration, and only the starting solution was administered to the target group (Control group).
  • Serum creatinine concentration (S-Cr) and blood urea nitrogen (S-BUN) were measured on the 7th day. Increased creatinine concentration, increased blood urea nitrogen, and increased crescent score due to anti-GBM nephritis were suppressed by administration of fat-derived MSCs, but were suppressed by administration of fat-derived MSCs and 5% (v / v) cryopreservation solution. The degree was low (Fig. 3).
  • mice Similar to Example 1, rats (WKY / NCrj, female) developed anti-GBM nephritis. Immediately after administration of anti-GBM mouse IgG, 2 ⁇ 10 6 cells of bone marrow-derived mesenchymal stem cells (bone marrow-derived MSC group) or adipose-derived mesenchymal stem cells (fat-derived MSC) were administered on the 2nd and 4th days. .. The cells were suspended in 2 mL of the starting solution (manufactured by Otsuka Pharmaceutical Factory) and 1.65% (v / v) cryopreservation solution (STEM-CELLBANKER® GMP Grade, containing 10% DMSO) and used for administration.
  • the starting solution manufactured by Otsuka Pharmaceutical Factory
  • v / v cryopreservation solution
  • the starting solution and 1.65% (v / v) cryopreservation solution were administered to the target group (Control group).
  • Serum creatinine concentration (S-Cr) and blood urea nitrogen (S-BUN) were measured on the 7th day. Increased creatinine concentration, increased blood urea nitrogen, and increased crescent score due to anti-GBM nephritis were suppressed by administration of fat-derived MSC and 1.65% (v / v) cryopreservation solution (Fig. 4).
  • mice Similar to Example 1, rats (WKY / NCrj, female) developed anti-GBM nephritis. Immediately after administration of anti-GBM mouse IgG, 2 ⁇ 10 6 cells of bone marrow-derived mesenchymal stem cells (bone marrow-derived MSC group) or adipose-derived mesenchymal stem cells (fat-derived MSC) were administered on the 2nd and 4th days. .. The cells were suspended in 2 mL of the starting solution (manufactured by Otsuka Pharmaceutical Factory) and 1.65% (v / v) cryopreservation solution (STEM-CELLBANKER® GMP Grade, containing 10% DMSO) and used for administration.
  • the starting solution manufactured by Otsuka Pharmaceutical Factory
  • v / v cryopreservation solution
  • CD25-positive regulatory T cells in the kidney can be increased, so that the function, structure, etc. of the diseased part such as the kidney can be remarkably improved.
  • This is expected to have an excellent therapeutic effect on renal diseases such as glomerulonephritis such as IgA nephropathy.
  • the mesenchymal stem cells contained in the regulatory T cell increasing agent of the present invention are unlikely to cause rejection even to allogeneic subjects, the donor cells prepared in advance are expanded and cryopreserved. Can be used. Therefore, there is an advantage that it is easy to commercialize and a stable and constant effect can be easily obtained as compared with the case where self-mesenchymal stem cells are prepared and used.

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PCT/JP2021/015093 2020-04-13 2021-04-09 腎臓中のｃｄ２５陽性の制御性ｔ細胞増加剤 Ceased WO2021210515A1 (ja)

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EP21788756.1A EP4137141A4 (en) 2020-04-13 2021-04-09 AGENT FOR INCREASING CD25-POSITIVE REGULATORY T CELLS IN THE KIDNEY
CN202180021798.6A CN115297877A (zh) 2020-04-13 2021-04-09 肾脏中cd25阳性调节性t细胞增加剂
JP2022515358A JPWO2021210515A1 (https=) 2020-04-13 2021-04-09
US17/918,390 US20230158076A1 (en) 2020-04-13 2021-04-09 Agent for increasing cd25-positive regulatory t cells in kidneys

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JP2014139214A (ja) * 2006-10-02 2014-07-31 Mesoblast International Srl 間葉系幹細胞とその用途
JP2015500810A (ja) * 2011-11-30 2015-01-08 アドバンスド セル テクノロジー、インコーポレイテッド 間葉系間質細胞及びその関連用途
JP2019510042A (ja) * 2016-03-28 2019-04-11 クック・ジェネラル・バイオテクノロジー・エルエルシー 生細胞組成物及び生細胞組成物に関連する方法

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