JP6509882B2 - 筋細胞パッチおよびその使用 - Google Patents
筋細胞パッチおよびその使用 Download PDFInfo
- Publication number
- JP6509882B2 JP6509882B2 JP2016547972A JP2016547972A JP6509882B2 JP 6509882 B2 JP6509882 B2 JP 6509882B2 JP 2016547972 A JP2016547972 A JP 2016547972A JP 2016547972 A JP2016547972 A JP 2016547972A JP 6509882 B2 JP6509882 B2 JP 6509882B2
- Authority
- JP
- Japan
- Prior art keywords
- construct
- cells
- heart failure
- heart
- contraction
- 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
- 210000000663 muscle cell Anatomy 0.000 title 1
- 210000004027 cell Anatomy 0.000 claims description 212
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 102
- 210000000555 contractile cell Anatomy 0.000 claims description 82
- 230000008602 contraction Effects 0.000 claims description 67
- 238000000034 method Methods 0.000 claims description 65
- 210000002950 fibroblast Anatomy 0.000 claims description 63
- 210000002216 heart Anatomy 0.000 claims description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 54
- 208000035475 disorder Diseases 0.000 claims description 50
- 206010019280 Heart failures Diseases 0.000 claims description 40
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 29
- 230000000747 cardiac effect Effects 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 21
- 230000002861 ventricular Effects 0.000 claims description 18
- 208000028867 ischemia Diseases 0.000 claims description 17
- 230000006872 improvement Effects 0.000 claims description 16
- 208000007814 Unstable Angina Diseases 0.000 claims description 15
- 230000003247 decreasing effect Effects 0.000 claims description 15
- 230000004064 dysfunction Effects 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 15
- 230000014509 gene expression Effects 0.000 claims description 15
- 238000002054 transplantation Methods 0.000 claims description 15
- 206010002388 Angina unstable Diseases 0.000 claims description 14
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 14
- 230000002107 myocardial effect Effects 0.000 claims description 14
- 210000004165 myocardium Anatomy 0.000 claims description 13
- 238000007634 remodeling Methods 0.000 claims description 13
- 208000007718 Stable Angina Diseases 0.000 claims description 12
- 230000010412 perfusion Effects 0.000 claims description 12
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 11
- 210000005240 left ventricle Anatomy 0.000 claims description 11
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims description 10
- 201000010046 Dilated cardiomyopathy Diseases 0.000 claims description 10
- 208000033774 Ventricular Remodeling Diseases 0.000 claims description 10
- 230000033001 locomotion Effects 0.000 claims description 10
- 208000031225 myocardial ischemia Diseases 0.000 claims description 10
- 208000000059 Dyspnea Diseases 0.000 claims description 9
- 206010013975 Dyspnoeas Diseases 0.000 claims description 9
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 claims description 8
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims description 8
- 238000012258 culturing Methods 0.000 claims description 8
- 238000007877 drug screening Methods 0.000 claims description 8
- 230000001360 synchronised effect Effects 0.000 claims description 8
- 206010024119 Left ventricular failure Diseases 0.000 claims description 7
- 230000002269 spontaneous effect Effects 0.000 claims description 7
- 206010003445 Ascites Diseases 0.000 claims description 6
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 6
- 206010010305 Confusional state Diseases 0.000 claims description 6
- 206010011703 Cyanosis Diseases 0.000 claims description 6
- 206010052337 Diastolic dysfunction Diseases 0.000 claims description 6
- 206010013974 Dyspnoea paroxysmal nocturnal Diseases 0.000 claims description 6
- 208000010496 Heart Arrest Diseases 0.000 claims description 6
- 206010019842 Hepatomegaly Diseases 0.000 claims description 6
- 206010030124 Oedema peripheral Diseases 0.000 claims description 6
- 208000004327 Paroxysmal Dyspnea Diseases 0.000 claims description 6
- 206010034568 Peripheral coldness Diseases 0.000 claims description 6
- 208000002151 Pleural effusion Diseases 0.000 claims description 6
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 6
- 206010039163 Right ventricular failure Diseases 0.000 claims description 6
- 206010071436 Systolic dysfunction Diseases 0.000 claims description 6
- 208000029078 coronary artery disease Diseases 0.000 claims description 6
- 208000002173 dizziness Diseases 0.000 claims description 6
- 208000018578 heart valve disease Diseases 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 206010029446 nocturia Diseases 0.000 claims description 6
- 208000005333 pulmonary edema Diseases 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 230000033764 rhythmic process Effects 0.000 claims description 6
- 210000000130 stem cell Anatomy 0.000 claims description 6
- 208000008203 tachypnea Diseases 0.000 claims description 6
- 206010043089 tachypnoea Diseases 0.000 claims description 6
- 238000006073 displacement reaction Methods 0.000 claims description 5
- 230000036581 peripheral resistance Effects 0.000 claims description 5
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 5
- 102000006573 Chemokine CXCL12 Human genes 0.000 claims description 4
- 108010008951 Chemokine CXCL12 Proteins 0.000 claims description 4
- 230000000977 initiatory effect Effects 0.000 claims description 4
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 4
- 206010007560 Cardiac failure high output Diseases 0.000 claims description 3
- UGPMCIBIHRSCBV-XNBOLLIBSA-N Thymosin beta 4 Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(C)=O UGPMCIBIHRSCBV-XNBOLLIBSA-N 0.000 claims description 3
- 102100035000 Thymosin beta-4 Human genes 0.000 claims description 3
- 241000700605 Viruses Species 0.000 claims description 3
- 238000010276 construction Methods 0.000 claims description 3
- 238000011161 development Methods 0.000 claims description 3
- 208000019271 high output heart failure Diseases 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 108010079996 thymosin beta(4) Proteins 0.000 claims description 3
- 101150013553 CD40 gene Proteins 0.000 claims description 2
- 108700020796 Oncogene Proteins 0.000 claims description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 2
- 208000008732 thymoma Diseases 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 description 61
- 210000002363 skeletal muscle cell Anatomy 0.000 description 25
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 24
- 230000004913 activation Effects 0.000 description 23
- 230000000302 ischemic effect Effects 0.000 description 23
- 230000006870 function Effects 0.000 description 22
- 239000000853 adhesive Substances 0.000 description 20
- 230000001070 adhesive effect Effects 0.000 description 20
- 210000005003 heart tissue Anatomy 0.000 description 15
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 15
- 239000000463 material Substances 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 230000035800 maturation Effects 0.000 description 12
- 108091006146 Channels Proteins 0.000 description 11
- 102100021337 Gap junction alpha-1 protein Human genes 0.000 description 9
- 210000004204 blood vessel Anatomy 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 8
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 8
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- 210000004351 coronary vessel Anatomy 0.000 description 8
- 208000014674 injury Diseases 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000010899 nucleation Methods 0.000 description 8
- 229920001778 nylon Polymers 0.000 description 8
- 108010048154 Angiopoietin-1 Proteins 0.000 description 7
- 102000009088 Angiopoietin-1 Human genes 0.000 description 7
- 102000008186 Collagen Human genes 0.000 description 7
- 108010035532 Collagen Proteins 0.000 description 7
- 108010069241 Connexin 43 Proteins 0.000 description 7
- 239000004677 Nylon Substances 0.000 description 7
- 229920001436 collagen Polymers 0.000 description 7
- 238000011049 filling Methods 0.000 description 7
- 210000002253 embryonic cardiomyocyte Anatomy 0.000 description 6
- 239000000990 laser dye Substances 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000001356 surgical procedure Methods 0.000 description 6
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000003205 diastolic effect Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 239000000017 hydrogel Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 5
- -1 polypropylene Polymers 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 206010002383 Angina Pectoris Diseases 0.000 description 4
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 4
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 4
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 4
- 206010061216 Infarction Diseases 0.000 description 4
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 4
- 239000000006 Nitroglycerin Substances 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 102100036859 Troponin I, cardiac muscle Human genes 0.000 description 4
- 101710128251 Troponin I, cardiac muscle Proteins 0.000 description 4
- 108010051583 Ventricular Myosins Proteins 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002592 echocardiography Methods 0.000 description 4
- 230000002500 effect on skin Effects 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 229960003711 glyceryl trinitrate Drugs 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 230000007574 infarction Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229920002223 polystyrene Polymers 0.000 description 4
- 238000002203 pretreatment Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
- 210000002536 stromal cell Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000012800 visualization Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010008479 Chest Pain Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 206010031123 Orthopnoea Diseases 0.000 description 3
- 229920000954 Polyglycolide Polymers 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 102000004987 Troponin T Human genes 0.000 description 3
- 108090001108 Troponin T Proteins 0.000 description 3
- 230000036982 action potential Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 206010003119 arrhythmia Diseases 0.000 description 3
- 230000006793 arrhythmia Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000003124 biologic agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 201000005890 congenital diaphragmatic hernia Diseases 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000011833 dog model Methods 0.000 description 3
- 210000001174 endocardium Anatomy 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 239000004744 fabric Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 208000012144 orthopnea Diseases 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229920000058 polyacrylate Polymers 0.000 description 3
- 239000004633 polyglycolic acid Substances 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 210000002235 sarcomere Anatomy 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 2
- 108091006112 ATPases Proteins 0.000 description 2
- 108010063503 Actinin Proteins 0.000 description 2
- 102000010825 Actinin Human genes 0.000 description 2
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
- 102400000345 Angiotensin-2 Human genes 0.000 description 2
- 101800000733 Angiotensin-2 Proteins 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- 102000004420 Creatine Kinase Human genes 0.000 description 2
- 108010042126 Creatine kinase Proteins 0.000 description 2
- 229920004934 Dacron® Polymers 0.000 description 2
- 206010012713 Diaphragmatic hernia Diseases 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical class CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 206010019909 Hernia Diseases 0.000 description 2
- 101000894966 Homo sapiens Gap junction alpha-1 protein Proteins 0.000 description 2
- 101000944277 Homo sapiens Inward rectifier potassium channel 2 Proteins 0.000 description 2
- 101000958741 Homo sapiens Myosin-6 Proteins 0.000 description 2
- 101001030243 Homo sapiens Myosin-7 Proteins 0.000 description 2
- 101001032038 Homo sapiens Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Proteins 0.000 description 2
- 101000694017 Homo sapiens Sodium channel protein type 5 subunit alpha Proteins 0.000 description 2
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000014429 Insulin-like growth factor Human genes 0.000 description 2
- 102100033114 Inward rectifier potassium channel 2 Human genes 0.000 description 2
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 2
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 2
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 2
- 102100038319 Myosin-6 Human genes 0.000 description 2
- 102100038934 Myosin-7 Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- 102100038718 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Human genes 0.000 description 2
- 239000004792 Prolene Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 102100027198 Sodium channel protein type 5 subunit alpha Human genes 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000004826 Synthetic adhesive Substances 0.000 description 2
- 208000008253 Systolic Heart Failure Diseases 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 102000013814 Wnt Human genes 0.000 description 2
- 108050003627 Wnt Proteins 0.000 description 2
- 206010000891 acute myocardial infarction Diseases 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 229950006323 angiotensin ii Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000003416 augmentation Effects 0.000 description 2
- 238000010009 beating Methods 0.000 description 2
- 238000009534 blood test Methods 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000002586 coronary angiography Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000003328 fibroblastic effect Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000002102 hyperpolarization Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 239000004800 polyvinyl chloride Substances 0.000 description 2
- 229920000915 polyvinyl chloride Polymers 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 238000011808 rodent model Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000003894 surgical glue Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003356 suture material Substances 0.000 description 2
- 239000003106 tissue adhesive Substances 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- CQVWXNBVRLKXPE-UHFFFAOYSA-N 2-octyl cyanoacrylate Chemical compound CCCCCCC(C)OC(=O)C(=C)C#N CQVWXNBVRLKXPE-UHFFFAOYSA-N 0.000 description 1
- LCSKNASZPVZHEG-UHFFFAOYSA-N 3,6-dimethyl-1,4-dioxane-2,5-dione;1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1.CC1OC(=O)C(C)OC1=O LCSKNASZPVZHEG-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- 208000025978 Athletic injury Diseases 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 201000000057 Coronary Stenosis Diseases 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- 206010011089 Coronary artery stenosis Diseases 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000032589 Diaphragmatic Congenital Hernias Diseases 0.000 description 1
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000035211 Heart Murmurs Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 206010049565 Muscle fatigue Diseases 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229920002201 Oxidized cellulose Polymers 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 108010038988 Peptide Hormones Proteins 0.000 description 1
- 102000015731 Peptide Hormones Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 102000013394 Troponin I Human genes 0.000 description 1
- 108010065729 Troponin I Proteins 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940030225 antihemorrhagics Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000003364 biologic glue Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229960004064 bumetanide Drugs 0.000 description 1
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000000512 collagen gel Substances 0.000 description 1
- 239000000515 collagen sponge Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 208000028659 discharge Diseases 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000010247 heart contraction Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000004115 mitral valve Anatomy 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 208000037891 myocardial injury Diseases 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229960001267 nesiritide Drugs 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 229940107304 oxidized cellulose Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 238000013146 percutaneous coronary intervention Methods 0.000 description 1
- 208000030613 peripheral artery disease Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000000622 polydioxanone Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical compound FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 239000002676 xenobiotic agent Substances 0.000 description 1
Images
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
- A61L27/3826—Muscle cells, e.g. smooth muscle 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
- A61K35/34—Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2292—Thymosin; Related peptides
-
- 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
- A61L27/3641—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 characterised by the site of application in the body
- A61L27/367—Muscle tissue, e.g. sphincter
-
- 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
- A61L27/3839—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 the site of application in the body
- A61L27/3873—Muscle tissue, e.g. sphincter
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C12N5/0062—General methods for three-dimensional culture
-
- 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
- C12N5/0657—Cardiomyocytes; Heart 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/64—Animal 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
-
- 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
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
- C12N2506/1315—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from cardiomyocytes
-
- 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
- C12N2513/00—3D culture
-
- 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
- C12N2527/00—Culture process characterised by the use of mechanical forces, e.g. strain, vibration
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Developmental Biology & Embryology (AREA)
- Botany (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Virology (AREA)
- Endocrinology (AREA)
Description
本願は、参照によりその全体が本明細書に援用される、2013年10月9日出願の米国仮特許出願第61/888882号の優先権を主張する。
本発明は、VAによって与えられた助成金番号1−101−BX001406−01A1の下で政府支援によってなされたものである。
(a)線維芽細胞含を含む3次元足場(3DFCS)の表面上に未成熟収縮細胞を播種して、収縮構築物を生成することと、
(b)条線を形成する成熟収縮細胞への未成熟収縮細胞の分化を促進する条件下で収縮構築物を培養することと、
を含む方法を提供する。
・形態学的に小さい細胞サイズ;
・筋原繊維密度の減少;
・電気生理学的に抑えられ/減少した活動電位振幅;
・MYH7(ベータミオシン重鎖)、MYH6(アルファミオシン重鎖)、SCN5A、GJA1(コネキシン43)、HCN4(過分極活性化K+チャネル)、KCNJ2(内向き整流性カリウムイオンチャネル)、SERCA2a(サルコ/小胞体(sarcoendoplasmic reticulum)ATPアーゼ)、アルファアクチニン、心臓トロポニンI(cTnI)、心臓トロポニンT(cTnT)の遺伝子および/またはタンパク質の発現の減少。
・形態学的に小さい細胞サイズ;
・筋原繊維密度の減少;
・電気生理学的に抑えられ/減少した活動電位振幅;
・MYH7(ベータミオシン重鎖)、MYH6(アルファミオシン重鎖)、SCN5A、GJA1(コネキシン43)、HCN4(過分極活性化K+チャネル)、KCNJ2(内向き整流性カリウムイオンチャネル)、SERCA2a(サルコ/小胞体ATPアーゼ)、アルファアクチニン、心臓トロポニンI(cTnI)、心臓トロポニンT(cTnT)の遺伝子および/またはタンパク質の発現の減少。
クラスI:いかなる活動でも制約を経験しない;通常の活動からの症状はない。
クラスII:活動にわずかに軽い制約がある;患者は安静時または軽度の労作時に快適である。
クラスIII:いかなる活動でも顕著な制約がある;患者は安静時にのみ快適である。
クラスIV:いかなる身体活動も不快感をもたらし、安静時に症状が起こる。
(a)収縮構築物を生成するための線維芽細胞含を含む3次元足場(3DFCS)の表面上に未成熟収縮細胞を播種することと、
(b)条線を形成する成熟収縮細胞への未成熟収縮細胞の分化を促進する条件下で、収縮構築物を培養することと、
を含む方法を提供する。
パッチの製造
播種方法
簡単に説明すると、懸濁液中の細胞に遠心力を適用する。3次元線維芽細胞構築物(3DFC)の表面上に細胞を押しやる/強いると、細胞をランダムだが均一に分布できる。ベースの構築物(3DFC)が細胞の移植および配置のための支持体ならびに適切な要件を提供すると、収縮力が生じる。最終「生成物」は、線維芽細胞が埋め込まれ、収縮細胞集団、この調製ではiPSC由来の(「未成熟」)心筋細胞が播種された分解性メッシュである。
誘導性ヒト多能性幹細胞(hiPSC)の播種密度は、0.3×106細胞/cm2〜2.4×106細胞/cm2の範囲であり、1.2×106細胞/cm2が理想である。
心臓パッチ用の出発材料は、ヒト皮膚線維芽細胞が埋め込まれた合成ビクリルメッシュを含む3DFCである。線維芽細胞は血管新生を示し、したがって、心臓への移植後、播種されたiPSC由来の心筋細胞集団に栄養サポートを提供する。発明者らのデータは、細胞比(皮膚線維芽細胞に対するiPSC由来の心筋細胞)が3:20〜1.2:1の範囲であり、1.2:2が理想であることを示している。
1. Thai, H. M., Juneman, E., Lancaster, J., Hagerty, T., Do, R., Castellano, L., Kellar, R., Williams, S., Sethi, G., Schmelz, M., Gaballa, M., & Goldman, S. (2009). Implantation of a three-dimensional fibroblast matrix improves left ventricular function and blood flow after acute myocardial infarction. Cell Transplant., 18(3), 283-295. PMC2739416:PM19558777. doi:10.3727/096368909788535004
2. Lancaster, J., Juneman, E., Hagerty, T., Do, R., Hicks, M., Meltzer, K., Standley, P., Gaballa, M., Kellar, R., Goldman, S., & Thai, H. (2010). Viable fibroblast matrix patch induces angiogenesis and increases myocardial blood flow in heart failure after myocardial infarction. Tissue Eng.Part A., 16(10), 3065-3073. PM20486785. doi:10.1089/ten.TEA.2009.0589
3. Lancaster, J. J., Arnce, S. A., Johnson, N. M., Juneman, E. B., Thai, H. M., Kellar, R. S., Vitorin, J. E., Burt, J. M., Bahl, J. J., & Goldman, S. (2010). In vivo evaluation of a biologically active cardiomyocyte seeded scaffold to treat chronic heart failure. [abstract]. Paper presented at the Heart Failure Society of America: 14th Annual Scientific Meeting, San Diego,CA. , 16(8) S45. doi:10.1016/j.cardfail.2010.06.155
4. Lancaster, J. J., Arnce, S. A., Johnson, N. M., Juneman, E. B., Thai, H. M., Kellar, R. S., Vitorin, J. E., Burt, J. M., Gaballa, M. A., Bahl, J. J., & Goldman, S. Tissue engineered scaffold seeded with cardiomyocytes improves cardiac function in rats with chronic ischemic heart failure disease. (Journal of Heart and Lung Transplantation).
Claims (40)
- 収縮構築物を調製するための方法であって、
(a)線維芽細胞を含む3次元足場(3DFCS)の表面上に未成熟収縮細胞を播種して、収縮構築物を生成することと、
(b)条線を形成する成熟収縮細胞への未成熟収縮細胞の発達を促進する条件下で前記収縮構築物を培養することと、
を含み、
前記収縮細胞が、多能性幹細胞に由来する心筋細胞である、
方法。 - 前記収縮構築物が約14〜240時間培養される、請求項1に記載の方法。
- 前記収縮構築物が48時間未満培養される、請求項1または2に記載の方法。
- 前記収縮構築物が約14〜36時間培養される、請求項1〜3のいずれか一項に記載の方法。
- 前記方法が、前記構築物と目的の化合物とを接触させることと、前記構築物の1つまたは複数の特徴に対する前記化合物の効果を決定することと、をさらに含む、請求項1〜4のいずれか一項に記載の方法。
- 前記方法が、前記構築物と目的の化合物とを接触させる前に、前記構築物の収縮を促進させる条件下で前記構築物を培養することを含む、請求項5に記載の方法。
- 収縮変位、収縮率、収縮同期性、および収縮速度のうちの1つまたは複数に対する前記化合物の効果が決定される、請求項6に記載の方法。
- 線維芽細胞を含む3次元足場(3DFCS)の表面に接着した収縮細胞またはその前駆体を含む構築物であって、
該構築物は、前記3DFCSの表面全体で自発的な同期収縮が可能であり、
前記収縮細胞が、1.3×105細胞/cm2〜2.95×106細胞/cm2の密度で前記構築物の表面上に播種され、前記3DFCS上の線維芽細胞と共に約1:15〜約6:1の比で前記3DFCSの表面上に存在し、
前記収縮細胞が、多能性幹細胞に由来する心筋細胞である、
構築物。 - 前記収縮細胞が、CD40および/またはHLAの発現を低減または排除するために操作される、請求項8に記載の構築物。
- 前記心筋細胞が未成熟心筋細胞を含む、請求項8または9に記載の構築物。
- 前記心筋細胞が成熟心筋細胞を含む、請求項8〜10のいずれか一項に記載の構築物。
- 前記未成熟心筋細胞および/または前記成熟心筋細胞が、1.3×105細胞/cm2〜2.7×106細胞/cm2の密度で前記構築物の表面上に播種され、前記収縮細胞が、前記3DFCS上の線維芽細胞と共に約1:7〜約3:1の比で前記3DFCSの表面上に存在する、請求項10または11に記載の構築物。
- 前記未成熟心筋細胞および/または前記成熟心筋細胞が、2.9×105細胞/cm2〜2.3×106細胞/cm2の総密度で前記構築物の表面上に播種される、請求項10または11に記載の構築物。
- 前記収縮細胞が前記構築物上に条線を形成する、請求項8〜13のいずれか一項に記載の構築物。
- 前記収縮細胞がヒト起源である、請求項8〜14のいずれか一項に記載の構築物。
- 血管前駆細胞をさらに含む、請求項8〜15のいずれか一項に記載の構築物。
- それを必要としている対象に移植するための請求項8〜16のいずれか一項に記載の構築物。
- 細胞収縮および/またはパッチレベルの収縮の開始前に移植される、請求項17に記載の構築物。
- パッチレベルの収縮の開始後に移植される、請求項17に記載の構築物。
- 前記移植が、障害を治療するのに有効な量の前記構築物と、前記障害に罹患している対象の心臓とを接触させることを含む、請求項17〜19のいずれか一項に記載の構築物。
- 前記障害が、虚血誘発性心不全、慢性心不全(CHF)、心不全を伴わない虚血、心筋症、拡張型心筋症(DCM)、心停止、うっ血性心不全、安定狭心症、不安定狭心症、心筋梗塞、冠動脈疾患、心臓弁膜症、虚血性心疾患、駆出率の低下、心筋灌流の低下、不適応な心臓リモデリング、不適応な左心室リモデリング、左心室機能の低下、左心不全、右心不全、後方不全、前方不全、収縮機能障害、拡張機能障害、全身血管抵抗の増加または減少、低拍出性心不全、高拍出性心不全、労作時呼吸困難、安静時呼吸困難、起座呼吸、頻呼吸、発作性夜間呼吸困難、めまい、精神錯乱、安静時の四肢の冷え、運動不耐性、易疲労感、末梢浮腫、夜間頻尿、腹水、肝腫大、肺水腫、チアノーゼ、心尖拍動の側方移動、奔馬調律、心雑音、傍胸骨拍動、および胸水からなる群から選択される、請求項20に記載の構築物。
- 前記障害がCHFを含む、請求項20に記載の構築物。
- 前記障害が虚血誘発性心不全を含む、請求項20に記載の構築物。
- 前記構築物を前記対象の心外膜に接着させる、請求項20〜23のいずれかに記載の構築物。
- 前記構築物を前記対象の左心室に接着させる、請求項20〜24のいずれか一項に記載の構築物。
- 心筋細胞の機能不全によって特徴付けられる障害を治療するための方法において使用するための請求項8〜25のいずれか一項に記載の構築物であって、
前記方法が、前記障害を有する患者を、前記障害を治療するのに有効な量で前記構築物と接触させることを含む、
構築物。 - 前記方法が、前記障害を治療するのに有効な量の前記構築物と、前記患者の心臓とを接触させることを含む、
請求項26に記載の構築物。 - 前記障害が、虚血誘発性心不全、慢性心不全(CHF)、心不全を伴わない虚血、心筋症、拡張型心筋症(DCM)、心停止、うっ血性心不全、安定狭心症、不安定狭心症、心筋梗塞、冠動脈疾患、心臓弁膜症、虚血性心疾患、駆出率の低下、心筋灌流の低下、不適応な心臓リモデリング、不適応な左心室リモデリング、左心室機能の低下、左心不全、右心不全、後方不全、前方不全、収縮機能障害、拡張機能障害、全身血管抵抗の増加または減少、低拍出性心不全、高拍出性心不全、労作時呼吸困難、安静時呼吸困難、起座呼吸、頻呼吸、発作性夜間呼吸困難、めまい、精神錯乱、安静時の四肢の冷え、運動不耐性、易疲労感、末梢浮腫、夜間頻尿、腹水、肝腫大、肺水腫、チアノーゼ、心尖拍動の側方移動、奔馬調律、心雑音、傍胸骨拍動、および胸水からなる群から選択される、請求項27に記載の構築物。
- 前記障害がCHFを含む、請求項27に記載の構築物。
- 前記障害が虚血誘発性心不全を含む、請求項27に記載の構築物。
- 前記構築物を前記患者の心外膜に接着させる、請求項27〜30のいずれかに記載の構築物。
- 前記構築物が、前記心外膜との接触時に収縮しない、請求項31に記載の構築物。
- 前記構築物が、前記心外膜との接触時に収縮している、請求項31に記載の構築物。
- 前記接触が、前記患者の左心室に前記構築物を接触させることを含む、請求項26〜33のいずれか一項に記載の構築物。
- 前記方法が、チモシンβ−4(TB4)、aktマウス胸腺腫ウイルス癌遺伝子ホモログ(ΑΚΤ1)、間質細胞由来因子−1アルファ(SDF−1)、および肝細胞増殖因子(HGF)のうちの1つまたは複数と前記患者の心臓とを接触させることをさらに含む、請求項26〜34のいずれか一項に記載の構築物。
- 前記治療が、左心室機能の改善、左心室拡張末期圧(EDP)の低下、心筋灌流の改善、心筋細胞による心臓壁の再構築、CHF対象における不適応な左心室リモデリングの逆進、拡張機能の改善、心室腔コンプライアンス、および心不全パラメータのうちの1つまたは複数を含み、
前記心不全パラメータは、E’(mm/秒)の増加、E/E’の減少、LV dP/dt(mmHg/秒)の増加およびTau(ミリ秒)の減少のうちの少なくとも1つを含む、
請求項26〜35のいずれか一項に記載の構築物。 - 前記構築物上の前記心筋細胞が前記患者の生来の心筋に電気的に結合する、請求項26〜36のいずれか一項に記載の構築物。
- 薬物スクリーニングのための方法であって、目的の化合物と請求項8〜37のいずれか一項に記載の構築物とを接触させることと、前記構築物の1つまたは複数の特徴に対する前記化合物の効果を決定することと、を含む方法。
- 前記方法が、前記構築物と目的の化合物とを接触させる前に、前記構築物の収縮を促進する条件下で前記構築物を培養することを含む、請求項38に記載の方法。
- 収縮変位、収縮率、収縮同期性、および収縮速度のうちの1つまたは複数に対する前記化合物の効果が決定される、請求項39に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361888882P | 2013-10-09 | 2013-10-09 | |
US61/888,882 | 2013-10-09 | ||
PCT/US2014/059688 WO2015054383A1 (en) | 2013-10-09 | 2014-10-08 | Muscle cell patches and uses therefor |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019071159A Division JP2019141065A (ja) | 2013-10-09 | 2019-04-03 | 筋細胞パッチおよびその使用 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016536103A JP2016536103A (ja) | 2016-11-24 |
JP6509882B2 true JP6509882B2 (ja) | 2019-05-08 |
Family
ID=52813614
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016547972A Active JP6509882B2 (ja) | 2013-10-09 | 2014-10-08 | 筋細胞パッチおよびその使用 |
JP2019071159A Pending JP2019141065A (ja) | 2013-10-09 | 2019-04-03 | 筋細胞パッチおよびその使用 |
JP2021084104A Pending JP2021121206A (ja) | 2013-10-09 | 2021-05-18 | 筋細胞パッチおよびその使用 |
JP2023106221A Pending JP2023123733A (ja) | 2013-10-09 | 2023-06-28 | 筋細胞パッチおよびその使用 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019071159A Pending JP2019141065A (ja) | 2013-10-09 | 2019-04-03 | 筋細胞パッチおよびその使用 |
JP2021084104A Pending JP2021121206A (ja) | 2013-10-09 | 2021-05-18 | 筋細胞パッチおよびその使用 |
JP2023106221A Pending JP2023123733A (ja) | 2013-10-09 | 2023-06-28 | 筋細胞パッチおよびその使用 |
Country Status (7)
Country | Link |
---|---|
US (2) | US10172976B2 (ja) |
EP (1) | EP3055028B1 (ja) |
JP (4) | JP6509882B2 (ja) |
AU (1) | AU2014331947B2 (ja) |
CA (1) | CA2927062A1 (ja) |
MX (1) | MX2016004616A (ja) |
WO (1) | WO2015054383A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11299714B2 (en) * | 2015-05-11 | 2022-04-12 | The Trustees Of Columbia University In The City Of New York | Engineered adult-like human heart tissue |
WO2018013851A1 (en) | 2016-07-13 | 2018-01-18 | The Trustees Of Columbia University | Bioreactor system for engineering tissues |
US11890395B2 (en) | 2017-06-16 | 2024-02-06 | Avery Therapeutics, Inc. | Three dimensional tissue compositions and methods of use |
AU2018297356A1 (en) | 2017-07-07 | 2020-02-27 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for improving cardiac function |
US11649424B2 (en) | 2017-07-28 | 2023-05-16 | The Trustees Of Columbia University In The City Of New York | Smart micro bioreactor platform for high throughput mechanical stimulation of cardiac microtissue |
WO2019222578A1 (en) * | 2018-05-18 | 2019-11-21 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for screening compounds for cardiac effects |
CN111787959A (zh) * | 2018-07-27 | 2020-10-16 | 国立大学法人长崎大学 | 用于消化道再生的片状细胞培养物 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5283058A (en) | 1990-08-30 | 1994-02-01 | The General Hospital Corporation | Methods for inhibiting rejection of transplanted tissue |
CA2453438C (en) * | 2001-07-12 | 2016-04-05 | Geron Corporation | Cells of the cardiomyocyte lineage produced from human pluripotent stem cells |
US7993922B2 (en) | 2002-10-18 | 2011-08-09 | Reliance Life Sciences Pvt. Ltd. | Three-dimensional tissue equivalent using macromass culture |
AU2005300638A1 (en) | 2004-11-05 | 2006-05-11 | Novosom Ag | Improvements in or relating to pharmaceutical compositions comprising an oligonucleotide as an active agent |
US20090169521A1 (en) * | 2007-12-31 | 2009-07-02 | Technion Research & Development Foundation Ltd. | Vascularized cardiac tissue and methods of producing and using same |
US9051550B2 (en) * | 2009-04-09 | 2015-06-09 | Arizona Board Of Regents, On Behalf Of The University Of Arizona | Cellular seeding and co-culture of a three dimensional fibroblast construct |
JP6124785B2 (ja) | 2011-02-28 | 2017-05-10 | ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. | 核酸多糖複合体 |
EP2766473A4 (en) * | 2011-10-12 | 2015-03-11 | Univ Pennsylvania | IN VITRO MICROPHYSIOLOGY SYSTEM FOR HIGH-RATE 3D TISSUE ORGANIZATION AND BIOLOGICAL FUNCTION |
-
2014
- 2014-10-08 MX MX2016004616A patent/MX2016004616A/es unknown
- 2014-10-08 EP EP14852537.1A patent/EP3055028B1/en active Active
- 2014-10-08 AU AU2014331947A patent/AU2014331947B2/en active Active
- 2014-10-08 US US15/028,606 patent/US10172976B2/en active Active
- 2014-10-08 WO PCT/US2014/059688 patent/WO2015054383A1/en active Application Filing
- 2014-10-08 JP JP2016547972A patent/JP6509882B2/ja active Active
- 2014-10-08 CA CA2927062A patent/CA2927062A1/en active Pending
-
2018
- 2018-12-20 US US16/228,017 patent/US11020510B2/en active Active
-
2019
- 2019-04-03 JP JP2019071159A patent/JP2019141065A/ja active Pending
-
2021
- 2021-05-18 JP JP2021084104A patent/JP2021121206A/ja active Pending
-
2023
- 2023-06-28 JP JP2023106221A patent/JP2023123733A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
EP3055028B1 (en) | 2024-01-03 |
MX2016004616A (es) | 2017-01-16 |
US11020510B2 (en) | 2021-06-01 |
US20190142999A1 (en) | 2019-05-16 |
CA2927062A1 (en) | 2015-04-16 |
EP3055028A1 (en) | 2016-08-17 |
JP2021121206A (ja) | 2021-08-26 |
US20210290823A1 (en) | 2021-09-23 |
EP3055028A4 (en) | 2017-04-05 |
JP2019141065A (ja) | 2019-08-29 |
WO2015054383A1 (en) | 2015-04-16 |
AU2014331947A1 (en) | 2016-05-05 |
US20160250384A1 (en) | 2016-09-01 |
AU2014331947B2 (en) | 2020-02-13 |
JP2023123733A (ja) | 2023-09-05 |
JP2016536103A (ja) | 2016-11-24 |
US10172976B2 (en) | 2019-01-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6509882B2 (ja) | 筋細胞パッチおよびその使用 | |
US20220306992A1 (en) | Cellular seeding and co-culture of a three dimensional fibroblast construct | |
ES2540242T3 (es) | Estructura tridimensional de tejido | |
US20160256497A1 (en) | Methods and compositions for treating congestive heart failure | |
Chachques et al. | Treatment of heart failure with autologous skeletal myoblasts | |
Lancaster et al. | Human induced pluripotent stem cell–derived cardiomyocyte patch in rats with heart failure | |
JP2023171773A (ja) | 心臓機能を改善するための組成物および方法 | |
US20210215674A1 (en) | Compositions and methods for screening compounds for cardiac side effects | |
US11980698B2 (en) | Muscle cell patches and uses therefor | |
TICHY | Effect of Human Basement Membrane on Cardiac Tissue Regeneration after Myocardial Infarction Development of Methods | |
ES2363754T3 (es) | Uso de tejido tridimensional cultivado para tratar la insuficiencia cardiaca congestiva. | |
AU2011235932A1 (en) | Use of cultured three-dimensional tissue for treating congestive heart failure |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171004 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180619 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180919 |
|
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: 20190305 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190403 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6509882 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: R3D02 |