JP6940837B2 - 間葉系幹細胞用培地 - Google Patents
間葉系幹細胞用培地 Download PDFInfo
- Publication number
- JP6940837B2 JP6940837B2 JP2016544246A JP2016544246A JP6940837B2 JP 6940837 B2 JP6940837 B2 JP 6940837B2 JP 2016544246 A JP2016544246 A JP 2016544246A JP 2016544246 A JP2016544246 A JP 2016544246A JP 6940837 B2 JP6940837 B2 JP 6940837B2
- Authority
- JP
- Japan
- Prior art keywords
- less
- medium
- stem cells
- mesenchymal stem
- medium according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 210000002901 mesenchymal stem cell Anatomy 0.000 title claims description 121
- 210000004027 cell Anatomy 0.000 claims description 85
- 238000012258 culturing Methods 0.000 claims description 38
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 32
- 210000002966 serum Anatomy 0.000 claims description 28
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 23
- 235000003704 aspartic acid Nutrition 0.000 claims description 23
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 20
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 16
- 239000004471 Glycine Substances 0.000 claims description 16
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 16
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 16
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 16
- 235000004279 alanine Nutrition 0.000 claims description 16
- 235000013922 glutamic acid Nutrition 0.000 claims description 16
- 239000004220 glutamic acid Substances 0.000 claims description 16
- 235000013930 proline Nutrition 0.000 claims description 16
- 235000004400 serine Nutrition 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 230000002062 proliferating effect Effects 0.000 claims description 12
- 150000003384 small molecules Chemical class 0.000 claims description 11
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 9
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 9
- 235000009582 asparagine Nutrition 0.000 claims description 9
- 229960001230 asparagine Drugs 0.000 claims description 9
- 102100022464 5'-nucleotidase Human genes 0.000 claims description 7
- 102100037241 Endoglin Human genes 0.000 claims description 7
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 claims description 7
- 101000881679 Homo sapiens Endoglin Proteins 0.000 claims description 7
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 claims description 7
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 claims description 7
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 6
- 238000012136 culture method Methods 0.000 claims description 6
- 238000000502 dialysis Methods 0.000 claims description 6
- 239000003550 marker Substances 0.000 claims description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 4
- 102000006354 HLA-DR Antigens Human genes 0.000 claims description 4
- 108010058597 HLA-DR Antigens Proteins 0.000 claims description 4
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 4
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 4
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 4
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 claims description 4
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 claims description 4
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 4
- 102100022338 Integrin alpha-M Human genes 0.000 claims description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 4
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 claims description 4
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 4
- 210000001185 bone marrow Anatomy 0.000 claims description 4
- 239000004475 Arginine Substances 0.000 claims description 3
- -1 CD79 Proteins 0.000 claims description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 3
- 239000004473 Threonine Substances 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 3
- 229960000310 isoleucine Drugs 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- 239000004474 valine Substances 0.000 claims description 3
- 239000002609 medium Substances 0.000 description 145
- 235000001014 amino acid Nutrition 0.000 description 50
- 229940024606 amino acid Drugs 0.000 description 50
- 150000001413 amino acids Chemical class 0.000 description 50
- 230000004069 differentiation Effects 0.000 description 29
- 210000001789 adipocyte Anatomy 0.000 description 18
- 230000035755 proliferation Effects 0.000 description 13
- 150000003839 salts Chemical group 0.000 description 11
- 230000001737 promoting effect Effects 0.000 description 9
- 239000000654 additive Substances 0.000 description 8
- 230000001186 cumulative effect Effects 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 230000004663 cell proliferation Effects 0.000 description 7
- 210000001612 chondrocyte Anatomy 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 210000000130 stem cell Anatomy 0.000 description 7
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000032683 aging Effects 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 210000001778 pluripotent stem cell Anatomy 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- 210000002449 bone cell Anatomy 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 238000012423 maintenance Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 5
- 241000282693 Cercopithecidae Species 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 239000007640 basal medium Substances 0.000 description 4
- 239000000306 component Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 230000032677 cell aging Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 3
- 229960003957 dexamethasone Drugs 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- JEFDYHWPYRIMCZ-UHFFFAOYSA-N 8-(3-methylbutyl)-3,7-dihydropurine-2,6-dione Chemical compound N1C(=O)NC(=O)C2=C1N=C(CCC(C)C)N2 JEFDYHWPYRIMCZ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010031264 Osteonecrosis Diseases 0.000 description 2
- 241000282579 Pan Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 241001515942 marmosets Species 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000002894 multi-fate stem cell Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000001988 somatic stem cell Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- PMYDPQQPEAYXKD-UHFFFAOYSA-N 3-hydroxy-n-naphthalen-2-ylnaphthalene-2-carboxamide Chemical compound C1=CC=CC2=CC(NC(=O)C3=CC4=CC=CC=C4C=C3O)=CC=C21 PMYDPQQPEAYXKD-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical group [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical class [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- MIJPAVRNWPDMOR-ZAFYKAAXSA-N L-ascorbic acid 2-phosphate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(OP(O)(O)=O)=C1O MIJPAVRNWPDMOR-ZAFYKAAXSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 229920002884 Laureth 4 Polymers 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000002804 Osteochondritis Diseases 0.000 description 1
- 201000009859 Osteochondrosis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 102100038126 Tenascin Human genes 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 244000078885 bloodborne pathogen Species 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 229910002090 carbon oxide Inorganic materials 0.000 description 1
- 210000003321 cartilage cell Anatomy 0.000 description 1
- 230000004956 cell adhesive effect Effects 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000012832 cell culture technique Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229940068840 d-biotin Drugs 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 210000000003 hoof Anatomy 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011655 sodium selenate Substances 0.000 description 1
- 229960001881 sodium selenate Drugs 0.000 description 1
- 235000018716 sodium selenate Nutrition 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000002444 unipotent stem cell Anatomy 0.000 description 1
Images
Classifications
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
- C12N5/0663—Bone marrow mesenchymal stem cells (BM-MSC)
-
- 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
- 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
- A61K35/55—Glands not provided for in groups A61K35/22 - A61K35/545, e.g. thyroids, parathyroids or pineal glands
-
- 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
- A61K35/56—Materials from animals other than mammals
-
- 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
-
- 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
- C12N5/0653—Adipocytes; Adipose tissue
-
- 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
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/32—Amino acids
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/70—Undefined extracts
- C12N2500/80—Undefined extracts from animals
- C12N2500/84—Undefined extracts from animals from mammals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Materials For Medical Uses (AREA)
Description
[1]少なくとも1種のアミノ酸の濃度が、グリシン5μM未満、アラニン5μM未満、セリン3μM未満、プロリン5μM未満、アスパラギン1μM未満、アスパラギン酸2μM未満、および/またはグルタミン酸3μM未満である、間葉系幹細胞用培地。
[2]グリシンが5μM未満である、上記[1]に記載の培地。
[3]グリシンが1μM未満である、上記[1]に記載の培地。
[4]アラニンが5μM未満である、上記[1]〜[3]のいずれかに記載の培地。
[5]アラニンが1μM未満である、上記[1]〜[3]のいずれかに記載の培地。
[6]セリンが3μM未満である、上記[1]〜[5]のいずれかに記載の培地。
[7]セリンが0.7μM未満である、上記[1]〜[5]のいずれかに記載の培地。
[8]プロリンが5μM未満である、上記[1]〜[7]のいずれかに記載の培地。
[9]プロリンが1μM未満である、上記[1]〜[7]のいずれかに記載の培地。
[10]アスパラギンが1μM未満である、上記[1]〜[9]のいずれかに記載の培地。
[11]アスパラギンが0.1μM未満である、上記[1]〜[9]のいずれかに記載の培地。
[12]アスパラギン酸が2μM未満である、上記[1]〜[11]のいずれかに記載の培地。
[13]アスパラギン酸が0.5μM未満である、上記[1]〜[11]のいずれかに記載の培地。
[14]グルタミン酸が3μM未満である、上記[1]〜[13]のいずれかに記載の培地。
[15]グルタミン酸が0.7μM未満である、上記[1]〜[13]のいずれかに記載の培地。
[16]グリシンが5μM未満、アラニンが5μM未満、セリンが3μM未満、プロリンが5μM未満、アスパラギンが1μM未満、アスパラギン酸が2μM未満、およびグルタミン酸が3μM未満である、上記[1]に記載の培地。
[17]グリシンが1μM未満、アラニンが1μM未満、セリンが0.7μM未満、プロリンが1μM未満、アスパラギンが0.1μM未満、アスパラギン酸が0.5μM未満、およびグルタミン酸が0.7μM未満である、上記[1]に記載の培地。
[18]低分子除去処理が施された血清または血清代替物を含有する、上記[1]〜[17]のいずれかに記載の培地。
[19]前記低分子除去処理が透析により行われる、上記[18]に記載の培地。
[20]血清がヒト血清である、上記[18]または[19]に記載の培地。
[21]非ヒト動物由来の成分を含まない、上記[1]〜[20]のいずれかに記載の培地。
[22]間葉系幹細胞が、ヒト間葉系幹細胞である上記[1]〜[21]のいずれかに記載の培地。
[23]間葉系幹細胞が、骨髄より採取されたものである上記[22]に記載の培地。
[24]上記[1]〜[23]のいずれかに記載の培地で間葉系幹細胞を培養する工程を含む、間葉系幹細胞の培養方法。
[25]間葉系幹細胞を培養する工程が、間葉系幹細胞を70日以上に亘り増殖させる工程である、上記[24]に記載の培養方法。
[26]上記[24]または[25]に記載の培養方法により得られる、細胞組成物。
[27]CD73、CD90およびCD105からなる群から選択される少なくとも1つのマーカーに陽性である、上記[26]に記載の細胞組成物。
[28]CD73、CD90およびCD105からなる群から選択される少なくとも1つのマーカーに陽性であり、かつ、CD45、CD34、CD14、CD11b、CD79、CD19およびHLA−DR陰性である、上記[26]に記載の細胞組成物。
[29]上記[24]または[25]に記載の培養方法により得られる、細胞医療用の細胞。
[30]グリシン、アラニン、セリン、プロリン、アスパラギン、アスパラギン酸およびグルタミン酸を添加せず、低分子除去処理が施された血清または血清代替物を含有する間葉系幹細胞用培地。
[31]ヒスチジン、イソロイシン、ロイシン、リジン、メチオニン、フェニルアラニン、トレオニン、トリプトファン、およびバリンを添加する、上記[30]に記載の培地。
[32]アルギニン、システイン、グルタミン、およびチロシンをさらに添加する、上記[31]に記載の培地。
1.細胞
LONZA社より購入した、正常ヒトドナーから採取、調製されたヒト間葉系幹細胞(カタログ番号:PT−2501)、および本発明者らが自主採取したヒト間葉系幹細胞(ロット番号:BM103〜104)を使用した。
間葉系幹細胞の培養においては、アミノ酸以外のDMEM(Dulbecco’s modified Eagle medium、GIBCO)を構成する成分(塩類、ビタミンなど)からなる培地(以下、「Zero培地」と表記される場合がある)、これに20種類のアミノ酸を添加した培地(以下、「Full培地」と表記される場合がある)、もしくは、グリシン、アラニン、セリン、プロリン、アスパラギン、アスパラギン酸およびグルタミン酸を除いた13種類のアミノ酸を添加した培地(以下、「−7培地」と表記される場合がある)、それぞれの培地に、透析により低分子を除去したFBS(fetal bovine serum、ライフテクノロジーズ社:26400−044)を10(v/v)%となるように添加し、使用した。
表1には、培養に使用した血清中における透析後の、上記7種アミノ酸の濃度、これらアミノ酸の、−7培地に添加した際の使用時の最終濃度、一般的な培地におけるこれらアミノ酸の濃度を示す。
間葉系幹細胞から脂肪細胞への分化は、脂肪分化誘導培地(10(v/v)% FBS(ライフテクノロジーズ社:26400−044)、0.01mg/mL インスリン(ナカライテスク社:19251−95)、1μM デキサメタゾン(シグマ社:D2915)、0.2mM インドメタシン(シグマ社:I7378)、0.5mM イソブチルメチルキサンチン(シグマ社:I7018)を添加した高グルコース含有DMEM培地(GIBCO))を使用して行った。脂肪細胞への分化後の培養は、脂肪維持培地(10(v/v)% FBS(ライフテクノロジーズ社:26400−044)、0.01mg/mL インスリン(ナカライテスク社:19251−95)を添加した高グルコース含有DMEM培地(GIBCO))を使用して行った。
間葉系幹細胞から脂肪細胞への分化培養および分化後の維持培養は、37℃、5% CO2雰囲気下のインキュベーター内で行った。
間葉系幹細胞を、6ウェルプレートの1ウェルあたり2x105細胞を播種し、間葉系幹細胞用培地にて100%コンフルエントになるまで培養を行った。続いて脂肪分化誘導培地へ培地交換し、3日間培養した後に、脂肪維持培地へ培地交換し、更に3日間培養を行った。この脂肪分化誘導培地と脂肪維持培地による計6日間の培養を、3サイクル合計18日間実施した。
培養後の細胞を10% ホルマリンにて固定した後、オイルレッドO染色に供した。続いて細胞を0.1% Thesit(登録商標)(ラウロマクロゴール)に溶解し、血清トリグリセリド測定キット(シグマ社:TR0100−1KT)にてトリグリセリド量を定量した。BCA(ビシンコニン酸)試薬を用いてタンパク質を定量し、タンパク質量当たりのトリグリセリド量を比較することで、細胞ごとの分化効率を検討した。
実施例1:−7培地での短期間培養による、間葉系幹細胞の細胞増殖促進効果(図1)
Zero培地、Full培地または−7培地でヒト間葉系幹細胞(ロット番号:OF3825)を7日間培養し、細胞数を評価した。細胞数の計測はCCKアッセイにより行った。市販のキットであるCell counting kit-8 (Dojindo)を使用し、キット付属の使用説明書に順じて操作を行った。CCKアッセイでは、OD450nm(縦軸)に細胞数が比例する。各培地につき3ウェルで評価を行い、各ウェルの値を○で、3ウェルの平均値を●で表した。Full培地で培養した場合に比べ、−7培地では間葉系幹細胞の増殖が顕著に促進されていることを見出した。
−7培地またはFull培地でヒト間葉系幹細胞(ロット番号:OF3825)を70日間培養し、それぞれの培地で培養したときの累積細胞数を計測した。継代時に、細胞をトリプシン処理で培養容器から剥がし、トリパンブルーと混和した後、細胞懸濁液を血球計算盤に供し、細胞数を計測した。細胞数の計測は、以下の実施例においても同様の方法で行った。Full培地で培養した場合に比べ、−7培地で培養した場合は累積細胞数が顕著に増大した。従って、−7培地は、間葉系幹細胞の長期に渡る増殖培養に適した培地であることが示された。
ロット番号:OF3853およびロット番号:OF4266のヒト間葉系幹細胞を、−7培地またはFull培地において30日間培養し、累積細胞数を計測した。両ロットのヒト間葉系幹細胞について、−7培地による顕著な増殖促進効果が認められた。
−7培地またはFull培地を用いて、ヒト間葉系幹細胞(ロット番号:BM103)を109日間培養し、それぞれ累積細胞数を計測した。−7培地での培養では、累積細胞数が頭打ちとはならずに、増殖し続けたのに対し、Full培地で培養した場合は、培養開始から70日目以降は累積細胞数がほぼ頭打ちとなった。Full培地での培養において、頭打ちとなるまでの培養により、最終的な累積細胞数は培養開始時の細胞数の1230倍であった。よって、Full培地による間葉系幹細胞の増殖培養可能な期間は、およそ70日間で、その場合の累積細胞数は培養開始時の細胞数の1230倍程度であることが明らかとなった。
−7培地またはFull培地で20日〜24日間培養したヒト間葉系幹細胞(ロット番号:BM103PN2(図5A)およびBM105PN2(図5B))を用いて、脂肪細胞、骨細胞または軟骨細胞への分化誘導を行った。骨細胞および軟骨細胞への分化に関しては、−7培地で培養した間葉系幹細胞は、Full培地で培養したものと比べ、同程度の分化効率を示した。脂肪細胞への分化に関しては、−7培地で培養した間葉系幹細胞は、Full培地で培養したものと比べ、分化効率が顕著に高かった(図5)。よって、−7培地は、間葉系幹細胞の骨細胞および軟骨細胞への分化に関しては従来の培地と同程度の分化能を維持しつつ、従来よりも効率のよい脂肪細胞への分化を可能とする培地であることが示された。
Claims (20)
- グリシンを5μM未満、アラニンを5μM未満、セリンを3μM未満、プロリンを5μM未満、アスパラギンを1μM未満、アスパラギン酸を2μM未満、およびグルタミン酸を3μM未満で含み、かつ、ヒスチジン、イソロイシン、ロイシン、リジン、メチオニン、フェニルアラニン、トレオニン、トリプトファン、バリン、アルギニン、システイン、グルタミンおよびチロシンを含む、間葉系幹細胞用培地。
- グリシンが1μM未満である、請求項1に記載の培地。
- アラニンが1μM未満である、請求項1に記載の培地。
- セリンが0.7μM未満である、請求項1に記載の培地。
- プロリンが1μM未満である、請求項1に記載の培地。
- アスパラギンが0.1μM未満である、請求項1に記載の培地。
- アスパラギン酸が0.5μM未満である、請求項1に記載の培地。
- グルタミン酸が0.7μM未満である、請求項1に記載の培地。
- グリシンが1μM未満、アラニンが1μM未満、セリンが0.7μM未満、プロリンが1μM未満、アスパラギンが0.1μM未満、アスパラギン酸が0.5μM未満、およびグルタミン酸が0.7μM未満である、請求項1に記載の培地。
- 低分子除去処理が施された血清または血清代替物を含有する、請求項1〜9のいずれか1項に記載の培地。
- 前記低分子除去処理が透析により行われる、請求項10に記載の培地。
- 血清がヒト血清である、請求項10または11に記載の培地。
- 非ヒト動物由来の成分を含まない、請求項1〜12のいずれか1項に記載の培地。
- 間葉系幹細胞が、ヒト間葉系幹細胞である請求項1〜13のいずれか1項に記載の培地。
- 間葉系幹細胞が、骨髄より採取されたものである請求項14に記載の培地。
- 請求項1〜15のいずれか1項に記載の培地で間葉系幹細胞を培養する工程を含む、間葉系幹細胞の培養方法。
- 間葉系幹細胞を培養する工程が、間葉系幹細胞を70日以上に亘り増殖させる工程である、請求項16に記載の培養方法。
- 請求項1〜15のいずれか1項に記載の培地を含み、かつ、請求項16または17に記載の培養方法により得られる、細胞組成物。
- CD73、CD90およびCD105からなる群から選択される少なくとも1つのマーカーに陽性である細胞を含む、請求項18に記載の細胞組成物。
- CD73、CD90およびCD105からなる群から選択される少なくとも1つのマーカーに陽性であり、かつ、CD45、CD34、CD14、CD11b、CD79、CD19およびHLA−DR陰性である細胞を含む、請求項18に記載の細胞組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2020081004A JP6944165B2 (ja) | 2014-08-21 | 2020-05-01 | 間葉系幹細胞用培地 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014168580 | 2014-08-21 | ||
JP2014168580 | 2014-08-21 | ||
PCT/JP2015/073349 WO2016027850A1 (ja) | 2014-08-21 | 2015-08-20 | 間葉系幹細胞用培地 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020081004A Division JP6944165B2 (ja) | 2014-08-21 | 2020-05-01 | 間葉系幹細胞用培地 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2016027850A1 JPWO2016027850A1 (ja) | 2017-06-01 |
JP6940837B2 true JP6940837B2 (ja) | 2021-09-29 |
Family
ID=55350791
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016544246A Active JP6940837B2 (ja) | 2014-08-21 | 2015-08-20 | 間葉系幹細胞用培地 |
JP2020081004A Active JP6944165B2 (ja) | 2014-08-21 | 2020-05-01 | 間葉系幹細胞用培地 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020081004A Active JP6944165B2 (ja) | 2014-08-21 | 2020-05-01 | 間葉系幹細胞用培地 |
Country Status (7)
Country | Link |
---|---|
US (1) | US10947508B2 (ja) |
EP (1) | EP3184627B1 (ja) |
JP (2) | JP6940837B2 (ja) |
KR (1) | KR102415441B1 (ja) |
CN (1) | CN106715683A (ja) |
CA (1) | CA2958533C (ja) |
WO (1) | WO2016027850A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3450548A4 (en) * | 2016-04-27 | 2019-11-20 | Rohto Pharmaceutical Co., Ltd. | MESENCHYMAL STEM CELL EXPRESSING AT LEAST ONE CELLULAR SURFACE MARKER SELECTED IN THE GROUP COMPRISED OF CD201, CD46, CD56, CD147 AND CD165 AND PROCESS FOR PREPARING THE SAME, PHARMACEUTICAL COMPOSITION CONTAINING THE MESENCHYMAL STEM CELL, AND PROCESS FOR PREPARING THE SAME |
EP3604503A4 (en) * | 2017-03-28 | 2020-12-30 | Ajinomoto Co., Inc. | ADDITIVE FOR DE-DIFFERENTIATION SUPPORT MEDIUM |
EP4144830A4 (en) | 2020-04-30 | 2024-06-12 | Oriental Yeast Co., Ltd. | STEM CELL MEDIUM AND STEM CELL CULTIVATION METHODS |
CN111979187B (zh) * | 2020-08-21 | 2022-04-08 | 遵义医科大学附属医院 | 一种抗人间充质干细胞衰老及增强其干性特征的方法 |
CN112300985B (zh) * | 2020-11-03 | 2022-07-01 | 中国人民解放军陆军军医大学第一附属医院 | 一种快速提升哺乳类动物骨髓间充质干细胞增殖效率的增殖培养基及增殖培养方法 |
KR20240125943A (ko) | 2021-12-27 | 2024-08-20 | 스미토모 파마 가부시키가이샤 | 신경능 세포의 배양 방법 및 제조 방법 |
WO2024158058A1 (ja) * | 2023-01-27 | 2024-08-02 | 株式会社Rainbow | 自動培養装置における細胞増殖制御方法 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4211766A (en) * | 1972-07-10 | 1980-07-08 | Ab Bonnierforetagen | Cancer associated polypeptide antigen compositions |
DE3702197C2 (de) | 1987-01-15 | 1993-12-23 | Kuebler Siegfried | Tennisschläger |
JP2006325445A (ja) * | 2005-05-24 | 2006-12-07 | Toyobo Co Ltd | 間葉系幹細胞増殖培地 |
WO2008049281A1 (fr) * | 2006-10-27 | 2008-05-02 | Beijing Institute Of Transfusion Medicine | Procédé de construction d'une construction de génie tissulaire hépatique et construction de génie tissulaire hépatique |
CN101755046B (zh) | 2007-07-20 | 2012-08-08 | 东国大学校产学协力团 | 采用间充质干细胞制备真皮乳头组织的方法 |
JP5257971B2 (ja) | 2007-10-25 | 2013-08-07 | 国立大学法人 千葉大学 | 胚性幹細胞から肝芽細胞を得る方法 |
EP2083071A1 (en) * | 2008-01-25 | 2009-07-29 | Cell Med Research GMBH | Medium for propagating and expanding stem cells |
EP2186883A1 (en) * | 2008-11-04 | 2010-05-19 | Fresenius Medical Care | An isolated multipotent mesenchymal stem cell from human adult glomeruli (hGL-MSC), a method of preparing thereof and uses thereof in the regenerative medicine of the kidney |
KR101211913B1 (ko) * | 2010-07-16 | 2012-12-13 | 주식회사 알앤엘바이오 | 양막유래 중간엽 줄기세포 배양을 위한 배지조성물 및 이를 이용한 양막유래 중간엽 줄기세포의 배양방법 |
US10000739B2 (en) | 2010-10-28 | 2018-06-19 | National University Corporation Kumamoto University | Method and culture medium for improving pluripotent stem cell differentiation inducing efficiency |
CN101984048A (zh) * | 2010-11-24 | 2011-03-09 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | 一种培养间充质干细胞的培养基 |
KR101138091B1 (ko) * | 2011-08-31 | 2012-04-24 | 세원셀론텍(주) | 중간엽 줄기세포 기본 배양 배지 조성방법, 중간엽 줄기세포 기본 배양 배지 및 이를 이용하여 배양분화된 세포치료제 |
AU2012346645B2 (en) | 2011-12-01 | 2015-08-27 | R Bio Co., Ltd. | Culture-medium composition for rejuvenating stem cells |
CN103060264B (zh) * | 2012-12-20 | 2015-01-21 | 上海市第十人民医院 | 一种干细胞培养基及其应用和干细胞培养方法 |
US9321995B2 (en) | 2012-12-20 | 2016-04-26 | Suzhou Biowisetech Co., Ltd. | Stem cell culture medium and its applications as well as a stem cell culture method |
CN103146755A (zh) * | 2013-02-28 | 2013-06-12 | 中国人民解放军第二军医大学 | 体外慢病毒介导bmp-2基因诱导滑膜间充质干细胞向软骨细胞分化的方法 |
-
2015
- 2015-08-20 WO PCT/JP2015/073349 patent/WO2016027850A1/ja active Application Filing
- 2015-08-20 CA CA2958533A patent/CA2958533C/en active Active
- 2015-08-20 CN CN201580044799.7A patent/CN106715683A/zh active Pending
- 2015-08-20 JP JP2016544246A patent/JP6940837B2/ja active Active
- 2015-08-20 KR KR1020177007657A patent/KR102415441B1/ko active IP Right Grant
- 2015-08-20 EP EP15833662.8A patent/EP3184627B1/en active Active
-
2017
- 2017-02-17 US US15/435,705 patent/US10947508B2/en active Active
-
2020
- 2020-05-01 JP JP2020081004A patent/JP6944165B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JPWO2016027850A1 (ja) | 2017-06-01 |
EP3184627A1 (en) | 2017-06-28 |
US10947508B2 (en) | 2021-03-16 |
JP6944165B2 (ja) | 2021-10-06 |
WO2016027850A1 (ja) | 2016-02-25 |
CN106715683A (zh) | 2017-05-24 |
EP3184627A4 (en) | 2018-04-18 |
US20170198258A1 (en) | 2017-07-13 |
CA2958533A1 (en) | 2016-02-25 |
JP2020124218A (ja) | 2020-08-20 |
CA2958533C (en) | 2023-03-14 |
KR20170042367A (ko) | 2017-04-18 |
KR102415441B1 (ko) | 2022-07-01 |
EP3184627B1 (en) | 2020-12-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6944165B2 (ja) | 間葉系幹細胞用培地 | |
JP6885870B2 (ja) | 間葉系幹細胞の細胞培養法 | |
RU2756561C2 (ru) | Среда для формирования колоний и её применение | |
BR112014020119A2 (pt) | cultura de células-tronco mesenquimais | |
Brouard et al. | G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving osteoclast-mediated bone resorption | |
KR20120008223A (ko) | 양막유래 중간엽 줄기세포 배양을 위한 배지조성물 및 이를 이용한 양막유래 중간엽 줄기세포의 배양방법 | |
Lei et al. | Heterogeneity of the biological properties and gene expression profiles of murine bone marrow stromal cells | |
WO2015004609A2 (en) | Adherent cells from placenta and use thereof in treatment of injured tendons | |
JP6713412B2 (ja) | 哺乳類筋肉由来の幹細胞 | |
JP2021040551A (ja) | 培地組成物、キット、間葉系幹細胞組成物の製造方法、間葉系幹細胞組成物、間葉系幹細胞、細胞培養上清および細胞外小胞 | |
JP6634822B2 (ja) | 幹細胞の培養用培地 | |
US20240182862A1 (en) | Method for producing mesenchymal stem cells | |
KR101753557B1 (ko) | 줄기세포 증식 향상 배지 조성물 및 줄기세포의 배양방법 | |
JP2006325445A (ja) | 間葉系幹細胞増殖培地 | |
Wang et al. | Epidermal growth factor can optimize a serum-free culture system for bone marrow stem cell proliferation in a miniature pig model | |
JP5714267B2 (ja) | 幹細胞の未分化維持剤及び増殖促進剤 | |
JP2020516241A (ja) | 筋肉由来の前駆細胞分化した細胞を取得する方法 | |
CN108517313B (zh) | 一种用于培养扩增牙髓干细胞的血清/血浆替代物 | |
Baouche et al. | Feline umbilical cord mesenchymal stem cells: isolation and in vitro characterization from distinct parts of the umbilical cord | |
WO2024195863A1 (ja) | 間葉系幹細胞増殖促進剤、間葉系幹細胞用培地、間葉系幹細胞及び培養上清 | |
WO2024117199A1 (ja) | 組成物、細胞の生産方法、細胞、細胞の培養方法および組成物の生産方法 | |
WO2024014517A1 (ja) | 細胞の培養方法、治療用組成物の製造方法及び治療用組成物 | |
US20240010986A1 (en) | Early mesenchymal stem cells with reduced aging and preserved stem cell ability, and culturing method therefor | |
JP6582044B2 (ja) | 凍結間葉系細胞の製造方法、及び、移植用治療材の製造方法 | |
Wen et al. | Multilineage potential research on metanephric mesenchymal stem cells of bama miniature pig |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180801 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180801 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190809 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20200204 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20200501 |
|
C116 | Written invitation by the chief administrative judge to file amendments |
Free format text: JAPANESE INTERMEDIATE CODE: C116 Effective date: 20200519 |
|
C22 | Notice of designation (change) of administrative judge |
Free format text: JAPANESE INTERMEDIATE CODE: C22 Effective date: 20200519 |
|
C22 | Notice of designation (change) of administrative judge |
Free format text: JAPANESE INTERMEDIATE CODE: C22 Effective date: 20210216 |
|
C13 | Notice of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: C13 Effective date: 20210420 |
|
C28A | Non-patent document cited |
Free format text: JAPANESE INTERMEDIATE CODE: C2838 Effective date: 20210420 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210614 |
|
C23 | Notice of termination of proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C23 Effective date: 20210713 |
|
C03 | Trial/appeal decision taken |
Free format text: JAPANESE INTERMEDIATE CODE: C03 Effective date: 20210817 |
|
C30A | Notification sent |
Free format text: JAPANESE INTERMEDIATE CODE: C3012 Effective date: 20210817 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210820 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6940837 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |