JP2005533535A - 血管新生が促進された移植片構成物 - Google Patents
血管新生が促進された移植片構成物 Download PDFInfo
- Publication number
- JP2005533535A JP2005533535A JP2004500789A JP2004500789A JP2005533535A JP 2005533535 A JP2005533535 A JP 2005533535A JP 2004500789 A JP2004500789 A JP 2004500789A JP 2004500789 A JP2004500789 A JP 2004500789A JP 2005533535 A JP2005533535 A JP 2005533535A
- Authority
- JP
- Japan
- Prior art keywords
- cell population
- composition
- matrix composition
- graft
- preselected
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 283
- 230000033115 angiogenesis Effects 0.000 title claims abstract description 17
- 210000004027 cell Anatomy 0.000 claims abstract description 200
- 239000011159 matrix material Substances 0.000 claims abstract description 170
- 210000002889 endothelial cell Anatomy 0.000 claims abstract description 142
- 210000001519 tissue Anatomy 0.000 claims abstract description 106
- 238000000034 method Methods 0.000 claims abstract description 71
- 210000004185 liver Anatomy 0.000 claims abstract description 52
- 210000002469 basement membrane Anatomy 0.000 claims abstract description 51
- 108010035532 Collagen Proteins 0.000 claims abstract description 36
- 102000008186 Collagen Human genes 0.000 claims abstract description 36
- 229920001436 collagen Polymers 0.000 claims abstract description 36
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims abstract description 33
- 210000004369 blood Anatomy 0.000 claims abstract description 31
- 239000008280 blood Substances 0.000 claims abstract description 31
- 239000000284 extract Substances 0.000 claims abstract description 27
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims abstract description 27
- 210000004876 tela submucosa Anatomy 0.000 claims abstract description 23
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 21
- 238000001727 in vivo Methods 0.000 claims abstract description 18
- 210000000130 stem cell Anatomy 0.000 claims abstract description 16
- 210000002919 epithelial cell Anatomy 0.000 claims abstract description 13
- 230000001737 promoting effect Effects 0.000 claims abstract description 10
- 210000002950 fibroblast Anatomy 0.000 claims abstract description 8
- 210000003716 mesoderm Anatomy 0.000 claims abstract description 6
- 238000000338 in vitro Methods 0.000 claims description 32
- 210000004204 blood vessel Anatomy 0.000 claims description 30
- 238000012258 culturing Methods 0.000 claims description 19
- 230000008439 repair process Effects 0.000 claims description 11
- 239000002243 precursor Substances 0.000 claims description 9
- 239000003102 growth factor Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 108010022901 Heparin Lyase Proteins 0.000 claims description 5
- 210000002966 serum Anatomy 0.000 claims description 4
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 3
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 3
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 3
- 230000010005 growth-factor like effect Effects 0.000 claims description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 3
- 210000003556 vascular endothelial cell Anatomy 0.000 claims description 3
- 230000002491 angiogenic effect Effects 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims 3
- 230000000977 initiatory effect Effects 0.000 claims 3
- 239000007943 implant Substances 0.000 claims 1
- 210000004413 cardiac myocyte Anatomy 0.000 abstract description 4
- 210000005009 osteogenic cell Anatomy 0.000 abstract description 3
- 210000003668 pericyte Anatomy 0.000 abstract description 3
- 210000002363 skeletal muscle cell Anatomy 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 24
- 238000002054 transplantation Methods 0.000 description 23
- 210000005228 liver tissue Anatomy 0.000 description 19
- 102000004190 Enzymes Human genes 0.000 description 13
- 108090000790 Enzymes Proteins 0.000 description 13
- 229940088598 enzyme Drugs 0.000 description 13
- 230000003902 lesion Effects 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 238000010494 dissociation reaction Methods 0.000 description 11
- 230000005593 dissociations Effects 0.000 description 11
- 108091005804 Peptidases Proteins 0.000 description 10
- 239000004365 Protease Substances 0.000 description 10
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 10
- 230000010261 cell growth Effects 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000029087 digestion Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 230000003196 chaotropic effect Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000006143 cell culture medium Substances 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 239000011536 extraction buffer Substances 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 210000003494 hepatocyte Anatomy 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 239000002738 chelating agent Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 235000013372 meat Nutrition 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 108010023728 Alloderm Proteins 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 108010082117 matrigel Proteins 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229940053363 periguard Drugs 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 108010009736 Protein Hydrolysates Proteins 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000003041 ligament Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 210000002435 tendon Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-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
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-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
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000004618 arterial endothelial cell Anatomy 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 238000012832 cell culture technique Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 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
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 108010026195 glycanase Proteins 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000011238 particulate composite Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 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
- A61L27/3886—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 comprising two or more cell types
-
- 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
- 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
- A61L27/3604—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 human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
-
- 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
- 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
- A61L27/3808—Endothelial 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
- 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
- A61L27/3813—Epithelial cells, e.g. keratinocytes, urothelial 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
- 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
- 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
- A61L27/383—Nerve cells, e.g. dendritic cells, Schwann cells
Abstract
Description
本発明は、マトリックス組成物由来の血管新生が促進された組織移植片、および病変組織または損傷組織を修復するためにその組織移植片を使用する方法に関する。特に、本発明は、組織移植片構成物の修復能を高めるために、内皮細胞および少なくとも一つの予め選択した追加の外因性細胞集団を接種したマトリックス組成物を含む、血管新生が促進された組織移植片を目的とする。
本発明は、肝臓の基底膜、その抽出物および水解物、ならびに脊椎動物の粘膜下組織以外の組織に由来する加工したコラーゲンからなる群から選択されるマトリックス組成物を含み、さらに追加の内皮細胞および少なくとも一つの予め選択した追加の外因性細胞集団を含む組織移植片構成物を目的とする。このマトリックス組成物に、内皮細胞および予め選択した外因性細胞集団を接種し、病変組織または損傷組織を修復するために使用する。本発明によれば、「損傷組織」とは、損傷し、裂傷し、切断され、または外科的に切除され、あるいは修復を必要とする部位を欠落している(例えば先天的欠損または先天的奇形)組織を意味する。
===肝臓基底膜組成物の調製===
本実験に使用する2mM EDTA緩衝カオトロピック溶液
140mM NaCl
5mM KCl
0.8mM MgSO4
0.4mM KH2HPO4
2mM EDTA
25mM NaHCO3
方法:
肝臓切片の調製:
−70℃で凍結した肝臓を、クリオマイクロトーンで厚さ約50μの切片にスライスした。次いで、この肝臓組織切片に、上記のカオトロピック溶液(2mM EDTA)による酵素処理(0.1%トリプシン)を供した。
これらの研究に使用した抽出バッファーは、4Mグアニジンおよび2M尿素を含有した(それぞれ、50mM Tris-HCl、pH7.4で調製)。肝臓の基底膜組織粉末を、フッ化フェニルメチルスルフォニル(PMSF)、N−エチルマレイミド、およびベンザミジン(プロテアーゼ阻害剤)を含む(それぞれ1mM)抽出バッファー(25% w/v)に懸濁し、4℃で24時間激しく撹拌した。その後、抽出混合液を4℃で30分間遠心(12,000×g)し、上清を回収した。不溶性の物質は、抽出バッファーで簡単に洗浄し、遠心し、洗浄液を元の上清と併せた。この上清を、30倍量の脱イオン水(72時間にわたり9回取替えた)でSpectrapor(MWCO 3,500、スペクトラム・メディカル・インダストリーズ(Spectrim Medical Industries)、ロサンゼルス、カリフォルニア州)のチューブで十分に透析した。いかなる不溶性の物質も除去するために、透析物を12,000×gで遠心し、この上清は直ちに使用しるか、もしくは凍結乾燥して保存した。
0.5Mの酢酸溶液(0.1%ペプシン含有)100mlに5gの粉末状組織を加え、4℃で72時間消化することにより、微粉砕した物質を部分的に消化した。部分的に消化した後、この懸濁液を4℃で20分間遠心(12,000rpm)し、不溶性のペレットを捨てた。この上清を、4℃で、0.01M酢酸を数回取り換えながら透析し(MWCO 3,500)、LBMの水解物にクロロホルム(900mlの0.01M酢酸に対し5mlのクロロホルム)を加えることにより、この溶液を滅菌した。無菌の0.01M酢酸をさらに2度取り換えてLBMの透析を続け、クロロホルムを除去した。その後、透析バッグの内容物を、無菌的な容器に無菌操作で移した。得られた流動組成物を4℃で保存した。
ゲル形態のLBMを調製するために、8mlの流動化LBMを、1.2mlの10×PBSバッファー(5mg/Lフェノールレッドを含む10×リン酸緩衝生理食塩水)(0.04N HCl(約1.6ml)を加え、pHを6.6〜7.4に調節し、pHが>8にシフトするまで0.05N NaOH(約1.2ml)を加えた)と混合した。最終量を水で12mlに調節した。
===内皮細胞の成長===
肝臓の基底膜組織を上記の通り調製する。様々な方法(γ線照射、過酢酸等)により滅菌した後、細胞増殖のための平坦な表面(50mm2)を作るために、この組織をポリプロピレンフレーム内に固定する。培地栄養素が、肝臓の基底膜組織の両方の表面へ届くように、このフレームを組織培養液に浸す。内皮細胞および平滑筋細胞を肝臓の基底膜に接種し、(3×104細胞/組織片)、次いで、37℃、5% CO2の95%エアインキュベーターに入れる。様々な時間培養した後、細胞を接種した肝臓の基底膜組織を、10%の中性緩衝ホルマリンで固定し、パラフィンに包埋して切片(6μm)を作成する。細胞増殖の特性を明らかにするために、様々な組織学染色および免疫組織化学的染色を実施する。これらの方法を用いて血管または血管様構造を観察する。
Claims (45)
- 病変組織または損傷組織の修復に使用するための、血管様構造を有する組織移植片構成物であって、
肝臓の基底膜、その抽出物および水解物、ならびに脊椎動物の粘膜下組織以外の組織に由来する加工したコラーゲンからなる群から選択されるマトリックス組成物と、
追加の内皮細胞および少なくとも一つの予め選択した追加の外因性細胞集団を含み、
該予め選択した追加の細胞集団が該組織移植片構成物における該血管様構造の形成開始を増強することを特徴とする、組織移植片構成物。 - 前記少なくとも一つの追加の細胞集団が、角化上皮細胞、非角化上皮細胞、および中胚葉由来細胞からなる群から選択される細胞集団を含むことを特徴とする、請求項1に記載の移植片構成物。
- 前記少なくとも一つの追加の細胞集団が、平滑筋細胞の集団を含むことを特徴とする、請求項1に記載の移植片構成物。
- 前記少なくとも一つの追加の細胞集団が、平滑筋細胞前駆細胞の集団を含むことを特徴とする、請求項1に記載の移植片構成物。
- 前記少なくとも一つの追加の細胞集団が、線維芽細胞を含むことを特徴とする、請求項1に記載の移植片構成物。
- さらにヘパリナーゼを含むことを特徴とする、請求項1に記載の移植片構成物。
- 血管内皮細胞由来増殖因子、血小板由来増殖因子、血小板由来増殖因子様分子、トランスフォーミング成長因子β、および血清増殖因子からなる群から選択される増殖因子をさらに含むことを特徴とする、請求項1に記載の移植片構成物。
- 前記マトリックス組成物に前記内皮細胞を接種した後に、該マトリックス組成物に前記予め選択した追加の細胞集団を接種すること特徴とする、請求項1に記載の移植片構成物。
- 前記マトリックス組成物に前記予め選択した追加の細胞集団を接種した後に、該マトリックス組成物に前記内皮細胞を接種することを特徴とする、請求項1に記載の移植片構成物。
- 前記マトリックス組成物に、前記内皮細胞と前記予め選択した追加の細胞集団とを同時にまたはほぼ同時に接種することを特徴とする、請求項1に記載の移植片構成物。
- 組織移植片構成物の血管新生をin vivoで促進する方法であって、
肝臓の基底膜、その抽出物および水解物、ならびに脊椎動物の粘膜下組織以外の組織に由来する加工したコラーゲンからなる群から選択されるマトリックス組成物に、内皮細胞集団および少なくとも一つの予め選択した追加の外因性細胞集団をin vitroで接種し該移植片構成物を形成し、該予め選択した追加の細胞集団により該組織移植片の該血管様構造の開始を増強する工程と、
脊椎動物の修復が必要な部位に該移植片構成物を移植する工程と、
を包含する方法。 - 前記少なくとも一つの追加の細胞集団が、角化上皮細胞、非角化上皮細胞、および中胚葉由来細胞からなる群から選択される細胞集団を含むことを特徴とする、請求項11に記載の方法。
- 前記少なくとも一つの追加の細胞集団が、平滑筋細胞集団を含むことを特徴とする、請求項11に記載の方法。
- 前記少なくとも一つの追加の細胞集団が、平滑筋細胞前駆細胞集団を含むことを特徴とする、請求項11に記載の方法。
- 前記少なくとも一つの追加の細胞集団が、線維芽細胞を含むことを特徴とする、請求項11に記載の方法。
- 前記移植片構成物が、さらにヘパリナーゼを含むことを特徴とする、請求項11に記載の方法。
- 前記移植片構成物が、血管内皮細胞由来増殖因子、血小板由来増殖因子、血小板由来増殖因子様分子、トランスフォーミング成長因子β、および血清増殖因子からなる群から選択される増殖因子をさらに含むことを特徴とする、請求項11に記載の方法。
- 前記移植片構成物を前記脊椎動物に移植する前に、in vitroで血管または血管様構造を形成させるのに十分な時間にわたって、前記マトリックス組成物上で前記内皮細胞を培養する工程をさらに包含する、請求項11に記載の方法。
- 前記マトリックス組成物に前記内皮細胞を接種した後に、該マトリックス組成物に前記予め選択した追加の細胞集団を接種することを特徴とする、請求項11に記載の方法。
- 前記マトリックス組成物に前記予め選択した追加の細胞集団を接種した後に、該マトリックス組成物に該内皮細胞を接種することを特徴とする、請求項11に記載の方法。
- 前記マトリックス組成物に、前記内皮細胞と前記予め選択した追加の細胞集団とを同時にまたはほぼ同時に接種することを特徴とする、請求項11に記載の方法。
- 前記マトリックス組成物に前記内皮細胞を接種した後に、該マトリックス組成物に前記予め選択した追加の細胞集団を接種することを特徴とする、請求項18に記載の方法。
- 前記マトリックス組成物に前記予め選択した追加の細胞集団を接種した後に、該マトリックス組成物に前記内皮細胞を接種することを特徴とする、請求項18に記載の方法。
- 前記マトリックス組成物に、前記内皮細胞と前記予め選択した追加の細胞集団とを同時に接種することを特徴とする、請求項18に記載の方法。
- 前記移植片構成物を移植する前に、前記内皮細胞も前記予め選択した追加の細胞集団も拡大(expand)させないことを特徴とする、請求項19、20または21のいずれか1項に記載の方法。
- in vitroで血管も血管様構造も形成しないで、前記内皮細胞を拡大させる(expand)のに十分な時間にわたって、前記マトリックス組成物上で該内皮細胞培養する工程と、
前記移植片構成物を前記脊椎動物に移植する前に、前記予め選択した追加の細胞集団を拡大させるのに十分な時間にわたって、該予め選択した追加の細胞集団を該マトリックス組成物上で培養する工程と、
をさらに包含する、請求項19、20または21のいずれか1項に記載の方法。 - in vitroで血管も血管様構造も形成しないで、前記内皮細胞を拡大させる(expand)のに十分な時間にわたって、該内皮細胞を前記マトリックス組成物上で培養する工程をさらに包含する、請求項19、20または21のいずれか1項に記載の方法。
- 前記移植片構成物を移植する前に、前記予め選択した追加の細胞集団を拡大(expand)させないことを特徴とする、請求項27に記載の方法。
- 前記移植片構成物を移植する前に、前記予め選択した細胞集団を拡大させる(expand)のに十分な時間にわたって、マトリックス組成物上で該予め選択した追加の細胞集団を培養する工程をさらに包含する、請求項19、20または21のいずれか1項に記載の方法。
- 前記移植片構成物を移植する前に、前記内皮細胞を拡大(expand)させないことを特徴とする、請求項29に記載の方法。
- 前記移植片構成物を移植する前に、前記予め選択した追加の細胞集団を拡大させる(expand)ことを特徴とする、請求項22、23または24のいずれか1項に記載の方法。
- 前記移植片構成物を移植する前に、前記予め選択した追加の細胞集団を拡大(expand)させないことを特徴とする、請求項22、23または24のいずれか1項に記載の方法。
- 病変組織または損傷組織の修復に使用するための、血管様構造を有する組織移植片構成物を調製する方法であって、
肝臓の基底膜、その抽出物および水解物、および脊椎動物の粘膜下組織以外の組織に由来する加工したコラーゲンからなる群から選択されるマトリックス組成物に、内皮細胞集団および少なくとも一つの予め選択した追加の外因性細胞集団をin vitroで接種し、該予め選択した追加の細胞集団により該組織移植片の該血管様構造の形成開始を増強する工程を包含する方法。 - 前記移植片構成物を前記脊椎動物に移植する前に、in vitroで血管または血管様構造を形成させるのに十分な時間にわたって、前記内皮細胞を前記マトリックス組成物上で培養する工程をさらに包含する、請求項33に記載の方法。
- 移植片構成物の血管新生をin vivoで促進する方法であって、
肝臓の基底膜、その抽出物および水解物、および脊椎動物の粘膜下組織以外の組織に由来する加工したコラーゲンからなる群から選択されるマトリックス組成物に、内皮細胞集団および少なくとも一つの予め選択した追加の外因性細胞集団をin vitroで接種し、該予め選択した追加の細胞集団により該組織移植片の血管新生の開始を増強する工程と、
血管または血管様構造の形成を誘導するのに十分な時間にわたって、該内皮細胞を該マトリックス組成物上でin vitroで培養する工程と、
脊椎動物の修復が必要な部位に前記移植片構成物を移植する工程と、
を包含する方法。 - 前記少なくとも一つの追加の細胞集団が、角化上皮細胞、非角化上皮細胞、および中胚葉由来細胞からなる群から選択される細胞集団を含むことを特徴とする、請求項35に記載の方法。
- 前記少なくとも一つの追加の細胞集団が、平滑筋細胞集団を含むことを特徴とする、請求項35に記載の方法。
- 前記少なくとも一つの追加の細胞集団が、平滑筋細胞前駆細胞の集団を含むことを特徴とする、請求35に記載の方法。
- 前記マトリックス組成物に前記内皮細胞を接種した後に、該マトリックス組成物に前記予め選択した追加の細胞集団を接種することを特徴とする、請求項35に記載の方法。
- 前記マトリックス組成物に前記予め選択した追加の細胞集団を接種した後に、該マトリックス組成物に前記内皮細胞を接種することを特徴とする、請求項35に記載の方法。
- 前記マトリックス組成物に、前記内皮細胞と前記予め選択した追加の細胞集団とを同時に接種することを特徴とする、請求項35に記載の方法。
- 病変組織または損傷組織の修復に使用するための血管新生した組織移植片構成物であって、
肝臓の基底膜、その抽出物および水解物、および脊椎動物の粘膜下組織以外の組織に由来する加工したコラーゲンからなる群から選択されるマトリックス組成物と、
追加の内皮細胞および少なくとも一つの予め選択した追加の外因性細胞集団を含み、
in vitroで血管または血管様構造を形成させるのに十分な時間にわたって、該内皮細胞を該マトリックス組成物上で培養したこと、かつ、
該予め選択した追加の細胞集団により該組織移植片の血管新生の開始を増強することを特徴とする、組織移植片構成物。 - 前記マトリックス組成物が、肝臓の基底膜を含有することを特徴とする、請求項1、2、3、4、5、6、7、8、9、10または42のいずれか1項に記載の組織移植片構成物。
- 前記マトリックス組成物が、脊椎動物の粘膜下組織以外の組織に由来する加工したコラーゲンを含有することを特徴とする、請求項1、2、3、4、5、6、7、8、9、10または42のいずれか1項に記載の組織移植片構成物。
- 患者の病変組織または損傷組織を治療する方法であって、該病変組織もしくは損傷組織を請求項1、2、3、4、5、6、7、8、9、10または42のいずれか1項に記載の組織移植片構成物で修復する工程を包含する方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37756502P | 2002-05-02 | 2002-05-02 | |
PCT/US2003/013555 WO2003092604A2 (en) | 2002-05-02 | 2003-05-01 | Vascularization enhanced graft constructs |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2005533535A true JP2005533535A (ja) | 2005-11-10 |
Family
ID=29401531
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004500789A Pending JP2005533535A (ja) | 2002-05-02 | 2003-05-01 | 血管新生が促進された移植片構成物 |
Country Status (8)
Country | Link |
---|---|
US (2) | US7795022B2 (ja) |
EP (1) | EP1503789A4 (ja) |
JP (1) | JP2005533535A (ja) |
CN (1) | CN1665527A (ja) |
AU (1) | AU2003243184C1 (ja) |
CA (1) | CA2483913C (ja) |
NZ (1) | NZ536564A (ja) |
WO (1) | WO2003092604A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010504149A (ja) * | 2006-09-21 | 2010-02-12 | ティシュー・ジェネシス・インコーポレーテッド | 細胞送達用マトリックス |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6485723B1 (en) * | 1995-02-10 | 2002-11-26 | Purdue Research Foundation | Enhanced submucosal tissue graft constructs |
US6696270B2 (en) | 1996-12-10 | 2004-02-24 | Purdue Research Foundation | Gastric submucosal tissue as a novel diagnostic tool |
AU732726B2 (en) * | 1996-12-10 | 2001-04-26 | Purdue Research Foundation | Biomaterial derived from vertebrate liver tissue |
US7919121B2 (en) * | 2002-01-11 | 2011-04-05 | Purdue Research Foundation | Biomaterial derived from vertebrate liver tissue |
JP2005524699A (ja) * | 2002-05-02 | 2005-08-18 | パーデュー・リサーチ・ファウンデーション | 血管新生が促進された移植片構成物 |
CA2483913C (en) * | 2002-05-02 | 2014-07-15 | Purdue Research Foundation | Vascularization enhanced graft constructs comprising basement membrane |
ATE472938T1 (de) * | 2002-05-02 | 2010-07-15 | Purdue Research Foundation | Transplantatkonstrukte mit verbesserter vaskularisierung |
AU2003258232A1 (en) * | 2002-08-20 | 2004-03-11 | Primezyme, Inc. | Food supplements from freeze-dried bovine tissues and method of ordering food supplements |
US7550004B2 (en) | 2002-08-20 | 2009-06-23 | Cook Biotech Incorporated | Endoluminal device with extracellular matrix material and methods |
US20040187877A1 (en) * | 2002-12-04 | 2004-09-30 | Badylak Stephen F. | Method for repair of liver tissue |
US20050031598A1 (en) * | 2002-12-10 | 2005-02-10 | Shulamit Levenberg | Engineering three-dimensional tissue structures using differentiating embryonic stem cells |
US7840263B2 (en) | 2004-02-27 | 2010-11-23 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression |
US7764995B2 (en) | 2004-06-07 | 2010-07-27 | Cardiac Pacemakers, Inc. | Method and apparatus to modulate cellular regeneration post myocardial infarct |
US8060219B2 (en) | 2004-12-20 | 2011-11-15 | Cardiac Pacemakers, Inc. | Epicardial patch including isolated extracellular matrix with pacing electrodes |
US8874204B2 (en) | 2004-12-20 | 2014-10-28 | Cardiac Pacemakers, Inc. | Implantable medical devices comprising isolated extracellular matrix |
US7981065B2 (en) | 2004-12-20 | 2011-07-19 | Cardiac Pacemakers, Inc. | Lead electrode incorporating extracellular matrix |
WO2006084040A2 (en) * | 2005-02-04 | 2006-08-10 | Massachusetts Institute Of Technology | Engineering vascularized muscle tissue |
MX2007010097A (es) | 2005-02-18 | 2007-10-10 | Synthasome Inc | Estructura sintetica para la preparacion de tejido blando. |
WO2006130851A2 (en) * | 2005-06-02 | 2006-12-07 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Prevascularized devices and related methods |
US20080279833A1 (en) * | 2007-05-10 | 2008-11-13 | Matheny Robert G | Laminate sheet articles for tissue regeneration |
US8679176B2 (en) | 2007-12-18 | 2014-03-25 | Cormatrix Cardiovascular, Inc | Prosthetic tissue valve |
US8257434B2 (en) | 2007-12-18 | 2012-09-04 | Cormatrix Cardiovascular, Inc. | Prosthetic tissue valve |
AU2010216095B2 (en) | 2009-02-18 | 2015-10-08 | Cormatrix Cardiovascular, Inc. | Compositions and methods for preventing cardiac arrhythmia |
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 |
US8883210B1 (en) | 2010-05-14 | 2014-11-11 | Musculoskeletal Transplant Foundation | Tissue-derived tissuegenic implants, and methods of fabricating and using same |
US10130736B1 (en) | 2010-05-14 | 2018-11-20 | Musculoskeletal Transplant Foundation | Tissue-derived tissuegenic implants, and methods of fabricating and using same |
US9352003B1 (en) | 2010-05-14 | 2016-05-31 | Musculoskeletal Transplant Foundation | Tissue-derived tissuegenic implants, and methods of fabricating and using same |
US8834928B1 (en) | 2011-05-16 | 2014-09-16 | Musculoskeletal Transplant Foundation | Tissue-derived tissugenic implants, and methods of fabricating and using same |
KR20140024905A (ko) | 2011-05-27 | 2014-03-03 | 코매트릭스 카디오바스컬라 인코포레이티드 | 멸균된 무세포성 세포외 기질 조성물 및 이의 제조 방법 |
US9446031B2 (en) | 2012-01-18 | 2016-09-20 | National University Of Singapore | Compositions and methods for neovascularization |
KR102101689B1 (ko) | 2013-02-08 | 2020-04-17 | 아셀, 인크. | 세포외 기질 재료로부터의 생리활성 겔의 제조 방법 |
CN105025939A (zh) * | 2013-03-15 | 2015-11-04 | 国立大学法人佐贺大学 | 心脏或血管组织型球体 |
CA2919374C (en) | 2013-07-30 | 2019-12-03 | Musculoskeletal Transplant Foundation | Acellular soft tissue-derived matrices and methods for preparing same |
US9878071B2 (en) | 2013-10-16 | 2018-01-30 | Purdue Research Foundation | Collagen compositions and methods of use |
WO2015143310A1 (en) | 2014-03-21 | 2015-09-24 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Methods for preparation of a terminally sterilized hydrogel derived from extracellular matrix |
US9238090B1 (en) | 2014-12-24 | 2016-01-19 | Fettech, Llc | Tissue-based compositions |
US11919941B2 (en) | 2015-04-21 | 2024-03-05 | Purdue Research Foundation | Cell-collagen-silica composites and methods of making and using the same |
WO2016187413A1 (en) | 2015-05-21 | 2016-11-24 | Musculoskeletal Transplant Foundation | Modified demineralized cortical bone fibers |
US10912864B2 (en) | 2015-07-24 | 2021-02-09 | Musculoskeletal Transplant Foundation | Acellular soft tissue-derived matrices and methods for preparing same |
US11052175B2 (en) | 2015-08-19 | 2021-07-06 | Musculoskeletal Transplant Foundation | Cartilage-derived implants and methods of making and using same |
ES2931299T3 (es) | 2017-03-02 | 2022-12-28 | Univ Pittsburgh Commonwealth Sys Higher Education | Hidrogel de matriz extracelular (ECM) y fracción soluble del mismo para su utilización en el tratamiento del cáncer |
CA3052489A1 (en) | 2017-03-02 | 2018-09-07 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Ecm hydrogel for treating esophageal inflammation |
US11739291B2 (en) | 2017-04-25 | 2023-08-29 | Purdue Research Foundation | 3-dimensional (3D) tissue-engineered muscle for tissue restoration |
ES2945740T3 (es) | 2017-05-05 | 2023-07-06 | Univ Pittsburgh Commonwealth Sys Higher Education | Aplicaciones oculares de vesículas unidas a matriz (MBV) |
US11826490B1 (en) | 2020-12-29 | 2023-11-28 | Acell, Inc. | Extracellular matrix sheet devices with improved mechanical properties and method of making |
CN114807005B (zh) * | 2022-04-09 | 2023-11-21 | 翌圣生物科技(上海)股份有限公司 | 使用动物尸体制备基质胶的方法 |
Family Cites Families (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US776596A (en) * | 1904-02-08 | 1904-12-06 | John F Welsh | Device for forming shoes. |
US5108424A (en) | 1984-01-30 | 1992-04-28 | Meadox Medicals, Inc. | Collagen-impregnated dacron graft |
US4829000A (en) * | 1985-08-30 | 1989-05-09 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Reconstituted basement membrane complex with biological activity |
US4883864A (en) | 1985-09-06 | 1989-11-28 | Minnesota Mining And Manufacturing Company | Modified collagen compound and method of preparation |
US5863531A (en) * | 1986-04-18 | 1999-01-26 | Advanced Tissue Sciences, Inc. | In vitro preparation of tubular tissue structures by stromal cell culture on a three-dimensional framework |
US4956178A (en) * | 1988-07-11 | 1990-09-11 | Purdue Research Foundation | Tissue graft composition |
US4902508A (en) * | 1988-07-11 | 1990-02-20 | Purdue Research Foundation | Tissue graft composition |
US5281422A (en) * | 1991-09-24 | 1994-01-25 | Purdue Research Foundation | Graft for promoting autogenous tissue growth |
US5641518A (en) * | 1992-11-13 | 1997-06-24 | Purdue Research Foundation | Method of repairing bone tissue |
US5275826A (en) | 1992-11-13 | 1994-01-04 | Purdue Research Foundation | Fluidized intestinal submucosa and its use as an injectable tissue graft |
US5352463A (en) * | 1992-11-13 | 1994-10-04 | Badylak Steven F | Tissue graft for surgical reconstruction of a collagenous meniscus and method therefor |
CA2119064A1 (en) * | 1993-03-17 | 1994-09-18 | Richard A. Berg | Dermal-epidermal in vitro test system |
US6475232B1 (en) * | 1996-12-10 | 2002-11-05 | Purdue Research Foundation | Stent with reduced thrombogenicity |
US6485723B1 (en) * | 1995-02-10 | 2002-11-26 | Purdue Research Foundation | Enhanced submucosal tissue graft constructs |
US5711969A (en) * | 1995-04-07 | 1998-01-27 | Purdue Research Foundation | Large area submucosal tissue graft constructs |
US5554389A (en) * | 1995-04-07 | 1996-09-10 | Purdue Research Foundation | Urinary bladder submucosa derived tissue graft |
US6419920B1 (en) * | 1995-10-25 | 2002-07-16 | Trans Karyotic Therapies, Inc. | Hybrid matrix implants and explants |
US6171344B1 (en) * | 1996-08-16 | 2001-01-09 | Children's Medical Center Corporation | Bladder submucosa seeded with cells for tissue reconstruction |
JP3816534B2 (ja) | 1996-08-16 | 2006-08-30 | チルドレンズ メディカル センター コーポレーション | 細胞を接種された組織再建術用膀胱粘膜下組織 |
US6206931B1 (en) * | 1996-08-23 | 2001-03-27 | Cook Incorporated | Graft prosthesis materials |
ES2213835T3 (es) * | 1996-09-16 | 2004-09-01 | Purdue Research Foundation | Injerto de tejidos intestinales submucosales para la reparacion de tejidos neurologicos. |
AU732726B2 (en) | 1996-12-10 | 2001-04-26 | Purdue Research Foundation | Biomaterial derived from vertebrate liver tissue |
US6099567A (en) * | 1996-12-10 | 2000-08-08 | Purdue Research Foundation | Stomach submucosa derived tissue graft |
JP4046358B2 (ja) * | 1996-12-10 | 2008-02-13 | パーデュー・リサーチ・ファウンデーション | 粘膜下組織抽出物 |
SK71399A3 (en) * | 1996-12-10 | 2000-05-16 | Purdue Research Foundation | Tubular submucosal graft constructs |
US5814328A (en) | 1997-01-13 | 1998-09-29 | Gunasekaran; Subramanian | Preparation of collagen using papain and a reducing agent |
WO1998052637A1 (en) * | 1997-05-23 | 1998-11-26 | Biosense, Inc. | Catheter with oblique lumen |
EP1056836B1 (en) * | 1998-02-27 | 2009-02-18 | Purdue Research Foundation | Submucosa gel compositions |
AU766719B2 (en) | 1998-09-11 | 2003-10-23 | Purdue Research Foundation | Enhanced submucosal tissue graft constructs |
US6918396B1 (en) * | 1998-12-01 | 2005-07-19 | Purdue Research Foundation | Method for vocal cord reconstruction |
AU4351000A (en) * | 1999-04-15 | 2000-11-02 | Research Foundation Of State University Of New York, The | Cellular matrix system and use thereof |
EP1207819B1 (en) | 1999-08-06 | 2009-03-04 | Cook Biotech, Inc. | Tubular graft construct |
ES2322662T3 (es) | 1999-12-22 | 2009-06-24 | Acell, Inc. | Composicion para regeneracion de tejidos. |
US6479064B1 (en) * | 1999-12-29 | 2002-11-12 | Children's Medical Center Corporation | Culturing different cell populations on a decellularized natural biostructure for organ reconstruction |
AU5159901A (en) | 2000-04-14 | 2001-10-30 | Univ Pittsburgh | Soft tissue and bone augmentation and bulking utilizing muscle-derived progenitor cells, compositions and treatments thereof |
HUP0300810A2 (hu) * | 2000-07-20 | 2003-08-28 | M.G.V.S. Ltd. | Mesterséges értranszplantátum, valamint ennek létrehozása és alkalmazása |
WO2002014480A2 (en) * | 2000-08-16 | 2002-02-21 | Duke University | Decellularized tissue engineered constructs and tissues |
US20040029270A1 (en) * | 2000-09-06 | 2004-02-12 | Lucie Germain | Vitro human angiogenesis model |
EP1404388B1 (en) | 2001-06-28 | 2013-10-23 | Cook Biotech, Inc. | Graft prosthesis devices containing renal capsule collagen |
US20030113302A1 (en) | 2001-08-31 | 2003-06-19 | Elena Revazova | Use of recipient endothelial cells for enhanced vascularization of tissue and tissue-engineered construct transplants |
JP2005524699A (ja) * | 2002-05-02 | 2005-08-18 | パーデュー・リサーチ・ファウンデーション | 血管新生が促進された移植片構成物 |
EP1585426A4 (en) | 2002-05-02 | 2006-09-20 | Cook Biotech Inc | WITH CELLS VACCINATED EXTRACELLULAR MATRIX TRANSPLANTS |
ATE472938T1 (de) * | 2002-05-02 | 2010-07-15 | Purdue Research Foundation | Transplantatkonstrukte mit verbesserter vaskularisierung |
CA2483913C (en) | 2002-05-02 | 2014-07-15 | Purdue Research Foundation | Vascularization enhanced graft constructs comprising basement membrane |
US8728463B2 (en) * | 2005-03-11 | 2014-05-20 | Wake Forest University Health Science | Production of tissue engineered digits and limbs |
-
2003
- 2003-05-01 CA CA2483913A patent/CA2483913C/en not_active Expired - Fee Related
- 2003-05-01 JP JP2004500789A patent/JP2005533535A/ja active Pending
- 2003-05-01 NZ NZ536564A patent/NZ536564A/en not_active IP Right Cessation
- 2003-05-01 EP EP03747631A patent/EP1503789A4/en not_active Ceased
- 2003-05-01 AU AU2003243184A patent/AU2003243184C1/en not_active Ceased
- 2003-05-01 CN CN038155729A patent/CN1665527A/zh active Pending
- 2003-05-01 WO PCT/US2003/013555 patent/WO2003092604A2/en active Application Filing
- 2003-05-02 US US10/428,355 patent/US7795022B2/en not_active Expired - Fee Related
-
2009
- 2009-09-10 US US12/557,176 patent/US8084048B2/en not_active Expired - Fee Related
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010504149A (ja) * | 2006-09-21 | 2010-02-12 | ティシュー・ジェネシス・インコーポレーテッド | 細胞送達用マトリックス |
Also Published As
Publication number | Publication date |
---|---|
CN1665527A (zh) | 2005-09-07 |
CA2483913C (en) | 2014-07-15 |
EP1503789A2 (en) | 2005-02-09 |
WO2003092604A3 (en) | 2004-06-03 |
WO2003092604A2 (en) | 2003-11-13 |
NZ536564A (en) | 2008-05-30 |
US8084048B2 (en) | 2011-12-27 |
AU2003243184B2 (en) | 2008-09-11 |
EP1503789A4 (en) | 2006-08-02 |
US7795022B2 (en) | 2010-09-14 |
AU2003243184A1 (en) | 2003-11-17 |
US20090324681A1 (en) | 2009-12-31 |
CA2483913A1 (en) | 2003-11-13 |
AU2003243184C1 (en) | 2009-04-09 |
US20030216812A1 (en) | 2003-11-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8084048B2 (en) | Vascularization enhanced graft constructs | |
US7776596B2 (en) | Vascularization enhanced graft constructs | |
CA2483908C (en) | Vascularization enhanced graft constructs | |
AU2021200593A1 (en) | Adipose tissue matrices | |
US6379710B1 (en) | Biomaterial derived from vertebrate liver tissue |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060428 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070612 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20070904 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20070911 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20070927 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20071004 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090303 |