JPWO2017126549A1 - 心疾患の治療のための移植材料 - Google Patents
心疾患の治療のための移植材料 Download PDFInfo
- Publication number
- JPWO2017126549A1 JPWO2017126549A1 JP2017562848A JP2017562848A JPWO2017126549A1 JP WO2017126549 A1 JPWO2017126549 A1 JP WO2017126549A1 JP 2017562848 A JP2017562848 A JP 2017562848A JP 2017562848 A JP2017562848 A JP 2017562848A JP WO2017126549 A1 JPWO2017126549 A1 JP WO2017126549A1
- Authority
- JP
- Japan
- Prior art keywords
- cells
- cell
- group
- adrcs
- heart disease
- 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.)
- Granted
Links
- 208000019622 heart disease Diseases 0.000 title claims abstract description 30
- 239000000463 material Substances 0.000 title claims description 36
- 238000011282 treatment Methods 0.000 title claims description 28
- 210000004027 cell Anatomy 0.000 claims description 190
- 238000000034 method Methods 0.000 claims description 30
- 210000000577 adipose tissue Anatomy 0.000 claims description 27
- 230000001172 regenerating effect Effects 0.000 claims description 26
- 108010049003 Fibrinogen Proteins 0.000 claims description 8
- 102000008946 Fibrinogen Human genes 0.000 claims description 8
- 229940012952 fibrinogen Drugs 0.000 claims description 8
- 239000000853 adhesive Substances 0.000 claims description 7
- 230000001070 adhesive effect Effects 0.000 claims description 7
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 claims description 5
- 210000001616 monocyte Anatomy 0.000 claims description 3
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 3
- 210000003954 umbilical cord Anatomy 0.000 claims description 3
- 210000003556 vascular endothelial cell Anatomy 0.000 claims description 3
- 210000002798 bone marrow cell Anatomy 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 abstract description 42
- 108010076365 Adiponectin Proteins 0.000 abstract description 33
- 102000011690 Adiponectin Human genes 0.000 abstract description 33
- 230000001225 therapeutic effect Effects 0.000 abstract description 13
- 230000002861 ventricular Effects 0.000 description 35
- 206010061216 Infarction Diseases 0.000 description 30
- 208000010125 myocardial infarction Diseases 0.000 description 22
- 241000700159 Rattus Species 0.000 description 19
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 18
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 18
- 230000007574 infarction Effects 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 15
- 210000001789 adipocyte Anatomy 0.000 description 13
- 230000004217 heart function Effects 0.000 description 13
- 238000005054 agglomeration Methods 0.000 description 12
- 230000002776 aggregation Effects 0.000 description 12
- 230000002107 myocardial effect Effects 0.000 description 11
- 210000004165 myocardium Anatomy 0.000 description 11
- 210000004351 coronary vessel Anatomy 0.000 description 10
- 230000004069 differentiation Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000013518 transcription Methods 0.000 description 10
- 230000035897 transcription Effects 0.000 description 10
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 9
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 9
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 229960005095 pioglitazone Drugs 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- 230000028327 secretion Effects 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 230000000747 cardiac effect Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 210000000130 stem cell Anatomy 0.000 description 7
- 238000002604 ultrasonography Methods 0.000 description 7
- 206010019280 Heart failures Diseases 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000012744 immunostaining Methods 0.000 description 6
- 238000001000 micrograph Methods 0.000 description 6
- 238000001356 surgical procedure Methods 0.000 description 6
- 102100033497 Adiponectin receptor protein 1 Human genes 0.000 description 5
- 102100032358 Adiponectin receptor protein 2 Human genes 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 101001135206 Homo sapiens Adiponectin receptor protein 1 Proteins 0.000 description 5
- 101000589401 Homo sapiens Adiponectin receptor protein 2 Proteins 0.000 description 5
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 5
- 230000003205 diastolic effect Effects 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 108010047303 von Willebrand Factor Proteins 0.000 description 5
- 102100036537 von Willebrand factor Human genes 0.000 description 5
- 229960001134 von willebrand factor Drugs 0.000 description 5
- 102100024154 Cadherin-13 Human genes 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108010066705 H-cadherin Proteins 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 4
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 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 4
- 229960002725 isoflurane Drugs 0.000 description 4
- 210000005240 left ventricle Anatomy 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 231100000241 scar Toxicity 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102000009123 Fibrin Human genes 0.000 description 3
- 108010073385 Fibrin Proteins 0.000 description 3
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 3
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 3
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 3
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 3
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 108090000190 Thrombin Proteins 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 210000004413 cardiac myocyte Anatomy 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229950003499 fibrin Drugs 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000000737 periodic effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229960004072 thrombin Drugs 0.000 description 3
- 102100022464 5'-nucleotidase Human genes 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 206010000891 acute myocardial infarction Diseases 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 230000006909 anti-apoptosis Effects 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
- 210000001367 artery Anatomy 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000007887 coronary angioplasty Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 210000002747 omentum Anatomy 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000013424 sirius red staining Methods 0.000 description 2
- 210000004003 subcutaneous fat Anatomy 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- 101710163391 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- -1 CD31 Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 240000006829 Ficus sundaica Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 229940127282 angiotensin receptor antagonist Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000002300 anti-fibrosis Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 230000004956 cell adhesive effect Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 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 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 229940028444 muse Drugs 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney 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
- 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
- A61K35/35—Fat tissue; Adipocytes; Stromal cells; Connective tissues
-
- 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
- A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor 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
- A61K35/48—Reproductive organs
- A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical 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
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/106—Fibrin; Fibrinogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Gynecology & Obstetrics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Vascular Medicine (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Botany (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
[材料と方法]
(1)脂肪組織由来再生細胞(ADRCs=Adipose derived regenerative cells)の調製
9週齢雌性LEW/Seaラットの両鼡径部から脂肪組織を採取した。脂肪組織を鋏で細かく刻み、0.1%のタイプIIコラゲナーゼ溶液中に懸濁し、37℃温浴槽で1時間震盪した。100μmおよび70μmのメッシュフィルターで濾過し、毎分1800回転10分間遠心分離した。沈査を培養培地(10%ウシ胎児血清、および抗生物質含有D-MEM)に懸濁したものを脂肪組織由来再生(間葉系前駆)細胞群(Adipose-derived Regenerative Cells: ADRCs)とした。これらは脂肪組織由来間葉系幹細胞および前駆細胞群を含んでいる。
脂肪組織からのADRCs抽出に引き続き、即座に、1片あたり5x106個のADRCsを含む細胞集塊を作製した。ADRCs細胞懸濁液140μlに対し、フィブリノーゲン60μlを添加してA液とし、また、培養液(10%ウシ胎児血清、抗生物質含有D-MEM)170μLに対し、トロンビン30mlを添加し充分に混和してB液とした。まず培養皿上にA液を滴下し、そこにB液を加え、移植に好適な形状に成形した後に、5%二酸化炭素雰囲気下、37℃の湿潤環境で5〜10分程保温して細胞同士を接着させることでADRCs細胞集塊を作製した。ADRCs細胞集塊の作製後、速やかに梗塞部位に移植した。
ADRCs細胞集塊を24、48、72、96、120、144時間培養した上澄液を採取し、酵素免疫抗体法(ELISA法)により上澄液中のアディポネクチン、VEGF、HGF、IL-6の分泌量をそれぞれ測定した。
ADRCs細胞集塊の凍結切片を作成し、4%パラホルムアルデヒドで固定後、オイルレッドO染色およびアディポネクチン免疫染色を施行した。
心筋梗塞モデルは、7週齢雌性LEW/Seaラットを用い、左冠動脈前下行枝結紮術により作製した。イソフルランの吸入麻酔人工呼吸下(1.5%イソフルラン、換気量4ml、110サイクル/分)に全身麻酔をした後、左開胸を行い、心臓を露出した。左冠動脈起始部から2〜3mmの部位を7-0プロリン糸で結紮した。冠動脈結紮術2週間後、ADRCs細胞集塊を先曲ピンセット上に載せて左室前壁の梗塞部位に滑らせ、静置した。無治療群に対しては、ADRCsを含まない安定化フィブリンを同様な処置で移植した。
冠動脈結紮術2週間後、ラットを5群に分けて以下の処置を行った。すなわちADRCs細胞集塊を左室前壁に移植した群(A群;n=26)、ピオグリタゾン(PGZ, 50mM)含有ADRCs細胞集塊を移植した群(AP群;n=26)、細胞集塊移植を行わない未治療群(S群;n=26)、ADRCsの左室前壁梗塞周囲への直接心筋内移植群(im群;n=6)および経左室冠動脈内移植群(ic群;n=6)である。手術後12日および56日後に組織学的評価、分子学的評価を行った。手術後1週間毎に心臓超音波検査にて心機能評価を行った。
イソフルランの吸入麻酔により抑制状態を得た後、14MHzトランスジューサーを備えた心臓超音波システムを用いて、乳頭筋レベルの左室短軸像を得た。左室の拡張末期径(LVEDd)および収縮末期径(LVESd)を測定した。測定は3回以上繰り返し、平均値を求めた。左室駆出率(EF%)は以下の式から算出した。
左室駆出率(EF)={(LVEDV-LVESV)/LVEDV}x100=(SV/LVEDV)x100
左室拡張末期容積(LVEDV)={7.0/(2.4+LVEDd)}xLVEDd3
左室収縮終末期容積(LVESV)={7.0/(2.4+LVEDs)}xLVEDs3
(8)組織学的評価
手術後14日目および56日目において、イソフルランの吸入深麻酔により抑制状態を得た後、拍動下に心臓を摘出した。左室を短軸方向にスライスしてコンパウンドに包理後、液体窒素中で凍結し、組織切片を作製した。ヘマトキシリン・エオジン染色、Picro-Sirius red染色、マッソン・トリクロム染色、オイルレッドO染色、アディポネクチン免疫染色、SMA免疫染色、von Willebrand factor免疫染色を施行した。線維化率をPicro-Sirius red染色の画像解析により求めた。梗塞周囲境界部位の生細胞サイズはヘマトキシリン・エオジン染色の1視野(400倍)の細胞短径を計測し、検体あたり10視野の平均値を算出した。また、von Willebrand factor免疫染色の1視野(400倍)あたりの毛細血管数を計測し、検体あたり5視野の平均値を算出した。
移植後14日目および56日目において、摘出した心臓サンプルを梗塞部(scar)、梗塞と正常部位の境界部(border)、非梗塞部(remote)に分けて、それぞれmRNA抽出をした。mRNAから逆転写反応によりcDNAを合成した。定量PCR法により血管内皮細胞増殖因子(VEGF)、アディポネクチン(APN)、アディポネクチン受容体-1(Adipo-R1)、アディポネクチン受容体-2(Adipo-R2)、T-カドヘリン(CDH-13)、および腫瘍壊死因子(TNF-α)の転写量を定量し、内在性コントロールであるグリセルアルデヒド3リン酸脱水素酵素(GAPDH)の転写量で除算した値を、各検体の正常値との比で表した。
データは平均値±標準誤差で表した。群間の比較はt検定にて行い、P値が0.05未満を有意差ありとした。生存率解析は、カプラン・マイヤー法により生存率を算出し、各実験群について、ログランク検定で有意差を求めた。
(1)ADRCs細胞集塊のサイトカイン分泌能および脂肪細胞への分化能
ADRCs細胞集塊(図1A)およびピオグリタゾン(PGZ)含有ADRCs細胞集塊を作製し、5%二酸化炭素雰囲気下、37℃の湿潤環境でそれぞれ144時間培養し、サイトカイン分泌能を検討した。ADRCs細胞集塊およびPGZ含有細胞集塊のアディポネクチン(APN)、VEGF、HGF、IL-6の分泌量は培養液においてそれぞれ経時的に増加した。特に144時間培養後のアディポネクチン濃度は、それぞれ21.7±0.9ng/5x106cells/dayおよび51±3.9ng/5x106cells/dayとなり、PGZ含有のADRCs細胞集塊培養液は、ADRCsのみの細胞集塊と比較して有意に高濃度であった(図1B)。
ADRCs細胞集塊の心筋への生着を検討するため、細胞集塊の作製後速やかにラット心筋への移植を行ったところ、数日から1週間後の細胞集塊は心表面に密着していた(図2A)。毛細血管で心筋との連絡が認められた(図2B)ことから、移植した細胞集塊は心筋へ生着することが確認できた。
慢性心筋梗塞モデルラットに対するADRCs細胞集塊移植後28日の心機能評価結果を図2に示した。心臓超音波検査における左室駆出率(EF)、左室収縮末期径(LVESd)、左室拡張期径(LVEDd)、拡張末期左室壁厚(LVAWD)を心機能の評価指標とした。モデルラットは冠動脈結紮術2週間後、5群に分けて以下の処置後に、試験を行った。すなわちADRCs細胞集塊を左室前壁に移植した群(A群)、ピオグリタゾン(PGZ)含有ADRCs細胞集塊を左室前壁に移植した群(AP群)、細胞集塊移植を行わない未治療群(S群)、ADRCs細胞の左室前壁梗塞周囲への直接心筋内移植群(im群)、および経左室冠動脈内移植群(ic群)である。
心筋梗塞モデルラットに対するADRCs細胞集塊移植後、14日目および56日目に、組織学的解析を施行した。未治療であるS群は強度の左室前壁菲薄化を認めた(図5A)が、A群(図5B)およびAP群(図5C)はS群、im群、ic群とに比して左室前壁が厚く、左室前壁組織が維持されていることを認めた(図5D)。梗塞サイズを定量したところ、統計学的有意差はないもののA群およびAP群における梗塞サイズはS群、im群、ic群と比して小さい傾向を示した(図5E)。さらに、梗塞部周縁の毛細血管密度を測定したところA群(図5G)およびAP群(図5H)ではS群(図5F)、im群、ic群と比して有意に高い毛細血管密度を示した(図5I)。
心筋梗塞モデルラットに対するADRCs細胞集塊移植14日および56日後、組織学的解析を施行した。各群の心筋梗塞部周縁における細胞径をヘマトキシリン・エオジン染色(図6A〜C)およびPAS染色(図6D〜F)により検出したところ、A群およびAP群における細胞短径はS群、im群、ic群と比して有意に低値であった(図6G)。以上の結果より、ADRCs細胞集塊移植は、残存心筋細胞に対し抗アポトーシスなどの保護作用を有する可能性が示唆された。
ADRCs細胞集塊移植後56日の心筋組織における心筋保護・抗炎症効果に関する検討結果を図7に示す。各群の梗塞部周縁の血管再生および心筋保護サイトカイン転写程度を評価したところ、AP群では他群と比して梗塞部周縁におけるアディポネクチン(APN)の転写量は有意に高かった(図7A)。またA群においても、S群よりも、APNの転写量は有意に高かった(図7A)。その他のAdipo-R1、Adipo-R2、CDH-13、VEGF、およびTNF-αの転写量には有意差を認められなかった(図7B〜F)。以上より、ADRCs細胞集塊にPGZを添加することにより、心筋梗塞後の心機能改善効果がさらに増強されている可能性が示唆された。
心筋梗塞モデルラットの左室前壁に移植されたADRCs細胞集塊は、移植後28日の左室前壁瘢痕領域に良好に生着しており(図8A)、移植部位でもアディポネクチン陽性であった(図8B)。生着した細胞集塊は持続的にアディポネクチンを分泌していたことが示唆された。また、比較対象とした、ADRCsの心筋内(図8C)および冠動脈内(図8D)移植を行った群においても移植後3日で心筋内に生着を認めた。
ADRCsの構成細胞を分析するためにフローサイトメトリー(FACS)を用いて細胞表面抗原を解析した。実施例1に示す方法によって、脂肪組織から抽出した新鮮なADRCsをFACS用染色液(5%ウシ胎児血清で補完したリン酸緩衝整理食塩水)に懸濁した。表面抗原マーカーとしてのCD11b、CD31、CD45、CD73、CD90に対するマウス抗体およびそれに対応するマウスIgG1アイソタイプを陰性マーカーとして用いた。細胞を室温にて30分間染色し、洗浄した後にフローサイトメトリー(BD FACS cant II instrument(BD Biosciences, San Jose, CA))を用いて解析した。
Claims (7)
- 分離された細胞を接着剤により接着させることにより得られる細胞集塊を含む、心疾患の治療のための移植材料。
- 分離された細胞が脂肪組織由来再生細胞、骨髄由来再生細胞、臍帯由来再生細胞、平滑筋由来再生細胞、多能性幹細胞およびそれに由来する再生細胞、血管内皮細胞、ならびに単球からなる群より選択される、請求項1に記載の移植材料。
- 分離された細胞が、PPARγアゴニストを作用させた脂肪組織由来再生細胞である、請求項1に記載の移植材料。
- 分離された細胞が培養されていないものである、請求項1から3のいずれかに記載の移植材料。
- 接着剤がフィブリノーゲンを含む、請求項1から4のいずれかに記載の移植材料。
- 請求項1から5のいずれかに記載の移植材料で、心疾患を罹患している対象の心表面を被覆することを特徴とする、心疾患の治療方法。
- 心疾患を罹患している対象が、移植材料が由来する細胞を採取した対象である、請求項6に記載の治療方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016008096 | 2016-01-19 | ||
JP2016008096 | 2016-01-19 | ||
PCT/JP2017/001538 WO2017126549A1 (ja) | 2016-01-19 | 2017-01-18 | 心疾患の治療のための移植材料 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2017126549A1 true JPWO2017126549A1 (ja) | 2018-11-08 |
JP6854519B2 JP6854519B2 (ja) | 2021-04-07 |
Family
ID=59362376
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017562848A Active JP6854519B2 (ja) | 2016-01-19 | 2017-01-18 | 心疾患の治療のための移植材料 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20210187031A1 (ja) |
EP (1) | EP3406255B1 (ja) |
JP (1) | JP6854519B2 (ja) |
CN (1) | CN108472319B (ja) |
SG (1) | SG11201806177QA (ja) |
WO (1) | WO2017126549A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109803665A (zh) * | 2016-10-18 | 2019-05-24 | 国立大学法人大阪大学 | 疾病治疗剂制备用试剂盒、疾病治疗剂和疾病治疗剂的制备方法 |
EP3750987A4 (en) | 2017-12-28 | 2021-11-10 | Kaneka Corporation | CELL POPULATION INCLUDING ADHESIVE STEM CELLS, ITS PRODUCTION PROCESS, AND PHARMACEUTICAL COMPOSITION |
CN111566205A (zh) | 2017-12-28 | 2020-08-21 | 株式会社钟化 | 包含贴壁性干细胞的细胞群、其制备方法、以及医药组合物 |
JP7217542B2 (ja) * | 2018-03-29 | 2023-02-03 | 国立大学法人 琉球大学 | 分化コントロール化合物を用いて造腫瘍性をもつおそれのある未分化iPS細胞等の混入を除去する方法 |
US20220162564A1 (en) | 2019-03-08 | 2022-05-26 | Kaneka Corporation | Mass culture of pluripotent stem cells |
JPWO2021045190A1 (ja) * | 2019-09-05 | 2021-03-11 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005047491A2 (en) * | 2003-11-10 | 2005-05-26 | Amgen Inc. | Methods of using g-csf mobilized c-kit+cells in the production of embryoid body-like cell clusters for tissue repair and in the treatment of cardiac myopathy |
WO2008153179A1 (ja) * | 2007-06-14 | 2008-12-18 | Akifumi Matsuyama | 脂肪組織由来多系統前駆細胞 |
JP2009542237A (ja) * | 2006-07-13 | 2009-12-03 | セルアーティス アーベー | ヒト胚盤胞由来幹細胞に由来する多能性心臓前駆細胞の新規の集団 |
WO2013162057A1 (ja) * | 2012-04-25 | 2013-10-31 | 独立行政法人理化学研究所 | 心筋指向性細胞を含む細胞製剤 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2364689T3 (es) * | 2005-05-25 | 2011-09-12 | Cytori Therapeutics, Inc. | Procedimiento de uso de células derivadas de tejido adiposo en el tratamiento de afecciones cardiovasculares. |
CN101517069A (zh) * | 2006-07-13 | 2009-08-26 | 塞拉帝思股份公司 | 由人类胚泡来源的干细胞衍生的多能心脏前体细胞新种群 |
EP2825638A4 (en) * | 2012-03-12 | 2015-11-25 | Univ Singapore | GENERATION OF ADIPOSE BROWN FABRIC (BAT) FROM MESENCHYMAL CELLS |
-
2017
- 2017-01-18 CN CN201780006848.7A patent/CN108472319B/zh active Active
- 2017-01-18 EP EP17741426.5A patent/EP3406255B1/en active Active
- 2017-01-18 SG SG11201806177QA patent/SG11201806177QA/en unknown
- 2017-01-18 WO PCT/JP2017/001538 patent/WO2017126549A1/ja active Application Filing
- 2017-01-18 JP JP2017562848A patent/JP6854519B2/ja active Active
- 2017-01-18 US US16/071,123 patent/US20210187031A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005047491A2 (en) * | 2003-11-10 | 2005-05-26 | Amgen Inc. | Methods of using g-csf mobilized c-kit+cells in the production of embryoid body-like cell clusters for tissue repair and in the treatment of cardiac myopathy |
JP2009542237A (ja) * | 2006-07-13 | 2009-12-03 | セルアーティス アーベー | ヒト胚盤胞由来幹細胞に由来する多能性心臓前駆細胞の新規の集団 |
WO2008153179A1 (ja) * | 2007-06-14 | 2008-12-18 | Akifumi Matsuyama | 脂肪組織由来多系統前駆細胞 |
WO2013162057A1 (ja) * | 2012-04-25 | 2013-10-31 | 独立行政法人理化学研究所 | 心筋指向性細胞を含む細胞製剤 |
Non-Patent Citations (1)
Title |
---|
FUKUSHIMA, S. ET AL.: "Choice of cell-delivery route for successful cell transplantation therapy for the heart", FUTURE CARDIOL, vol. 9, no. 2, JPN6017005549, 2013, pages 215 - 27, XP055400668, ISSN: 0004364813 * |
Also Published As
Publication number | Publication date |
---|---|
EP3406255C0 (en) | 2023-06-07 |
US20210187031A1 (en) | 2021-06-24 |
JP6854519B2 (ja) | 2021-04-07 |
EP3406255A1 (en) | 2018-11-28 |
CN108472319A (zh) | 2018-08-31 |
WO2017126549A1 (ja) | 2017-07-27 |
CN108472319B (zh) | 2021-12-28 |
SG11201806177QA (en) | 2018-08-30 |
EP3406255B1 (en) | 2023-06-07 |
EP3406255A4 (en) | 2019-08-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6854519B2 (ja) | 心疾患の治療のための移植材料 | |
US20180214486A1 (en) | Bone marrow derived cd271 precursor cells for cardiac repair | |
JP6555691B2 (ja) | 間葉系幹細胞の賦活化剤、賦活化された間葉系幹細胞およびその製造方法 | |
US11660317B2 (en) | Compositions comprising cardiosphere-derived cells for use in cell therapy | |
JP2007525422A (ja) | 心臓血管疾患の治療における脂肪組織由来細胞の使用方法 | |
JP6781973B2 (ja) | 腎臓病進行抑制細胞シート組成物、その製造方法、及び、それを用いた腎臓病進行抑制方法 | |
JP6618066B2 (ja) | 線維芽細胞を含む心臓疾患を治療するための注射用組成物、及び治療用線維芽細胞の製造方法 | |
US20160346331A1 (en) | Cardiac tissue-derived cells | |
US20220233599A1 (en) | Pharmaceutical composition | |
US11963983B2 (en) | Methods of cardiac repair | |
WO2019104466A1 (en) | Methods of producing populations of mesenchymal stem cells from peripheral blood and uses thereof | |
WO2022123958A1 (en) | Pharmaceutical composition for use in prevention and treatment of liver fibrosis and/or liver cirrhosis, comprising adipose-derived regenerative cells (adrcs) | |
Bank | TRANSPLANTATION AND CELLULAR ENGINEERING | |
Martens | Novel Platforms for Cardiovascular Repair |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180720 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20191206 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20201013 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20201203 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210208 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210226 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210309 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6854519 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20210208 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |