片狀間葉幹細胞於心肌組織工程上之應用｜國立清華大學博碩士論文庫

簡易檢索 / 詳目顯示

回結果列表

研究生：	陳俊宏 Chun-Hung Chen
論文名稱：	片狀間葉幹細胞於心肌組織工程上之應用 Novel Mesenchymal-Stem-Cell Sheet for Myocardial Regenerative Medicine
指導教授：	宋信文 Hsing-Wen Sung
口試委員:
學位類別：	博士 Doctor
系所名稱：	工學院 - 化學工程學系 Department of Chemical Engineering
論文出版年：	2007
畢業學年度：	96
語文別：	英文
論文頁數：	103
中文關鍵詞：	細胞片、心肌梗塞、血管新生、間葉幹細胞、細胞治療術
外文關鍵詞：	Cell sheet, myocardial infarction, angiogenesis, mesenchymal stem cell, cell therapy
相關次數：	點閱：3 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

心肌梗塞是缺血性心臟病中最致命與最典型的病症，亦是工業化國家中首要的死因。然而目前的治療方式只有傳統的冠狀動脈繞道手術、心導管氣球擴張術、左心室輔助裝置、心室補綴片成形術或心臟移植等，每一種皆有其風險及限制。根據以上的文獻回顧及先前的研究結果，我們可以推測細胞片組織工程的特點對於運用成體幹細胞治療心肌梗塞的再生醫學技術上，將可改進了許多傳統細胞注射治療及補綴片修補技術無法解決的問題。故本論文主要的目的，為應用溫度敏感性高分子甲基纖維素的成膠特性，研發一新穎片狀活細胞生產系統，並以此生產成體幹細胞片(MSC sheet)做為細胞片組織工程運用於心肌治療上。
在體外實驗裡，我們探討了不同黏度值的MC，於室溫下溶解在不同的鹽類組成或PBS及細胞培養基，並探討其成膠之溫度以及滲透壓。其主要原理是利用鹽析作用來增加MC的疏水性作用力，降低其成膠溫度以符合培養細胞的需求。其鹽類組成包括了NaCl, Na2SO4, Na3PO4。此外我們也探討了利用collagen、poly-L-lysine 等生物巨分子修飾成膠後的MC水膠表面，並在修飾後，進一步分析其成膠溫度與其成膠後的表面性質的改變以及對細胞的生物相容性質。為了符合細胞培養的環境，只有在37℃下能夠形成膠狀的高分子黏度與鹽類的條件並且符合其生理特性者，才會被挑出來做後續的研究。
在第一部份的體內實驗裡，我們利用外科手術方式將老鼠左冠狀動脈(left coronary artery)結紮後，製造出急性心肌梗塞。然後將片狀的MSC sheet注射到心肌梗塞區域的邊緣，探討幹細胞片在壞死的心肌區域中，其增生及分化情形，並對於左心室及整體心臟功能的影響進行評估。實驗中，我們以生理實驗水、sham operated做為空白對照組，而以傳統繼代培養所獲得的MSCs為正對照組。在急性心肌梗塞症狀出現25分鐘後進行注射。並在心肌注射後的四週、八週及十二週，以心臟超音波，心電圖及心室壓力量測以觀察左心室與心臟整體功能的變化情形。注射十二週後取樣，取樣後，我們以巨觀觀察及組織切片來分析壞死心肌內細胞的分佈及其植入細胞的分化後的特性。
在第二部份的體內實驗裡，我們將先利用外科手術方式將老鼠左冠狀動脈(left coronary artery)結紮後，四周後製造出慢性心肌梗塞產生心室肥大的症狀。然後將夾有片狀的MSC sheet的去細胞牛心包膜利用EVCPP置換其擴大的心室部位。實驗中，我們將以sham operated及去細胞牛心包膜做為空白對照組，而以種有非片狀MSCs的去細胞牛心包膜為正對照組。我們於植入四週後取樣，並在執行EVCPP前以及取樣的前一天，同第三部份實驗分析方法，以觀察左心室及整體心臟功能，並進一步利用組織切片分析其細胞分化與血管新生的情形。

Myocardial infarction (MI) progresses from the acute death of cardiomyocytes and the infiltration of inflammatory cells into granulation, followed by scars. Recently, the identification of stem cells capable of contributing to tissue regeneration has raised the possibility that cell therapy could be employed for repair of damaged myocardium. It was shown that cell transplantation via local intramuscular injection is a promising therapy for patients with myocardial infarction. However, following injection of the dissociated cells, retention of the transplanted cells in the injected area remains a central issue. These facts can be deleterious to cell-transplantation therapy.
The purpose of study I was to evaluate using a thermoreversible hydrogel system, treated as a coating on tissue culture polystyrene (TCPS) dishes and developed for harvesting living cell sheets. The hydrogel system was prepared by simply pouring aqueous methylcellulose (MC) solutions blended with distinct salts on TCPS dishes at 20℃. To improve cell attachments, the MC/PBS hydrogel at 37℃ was evenly spread with a neutral aqueous collagen at 4℃. The spread aqueous collagen gradually reconstituted with time and thus formed a thin layer of collagen (the MC/PBS/Collagen hydrogel). After cells reached confluence, a continuous monolayer cell sheet was formed on the surface of the MC/PBS/Collagen hydrogel. Additionally, the developed hydrogel system can be used for culturing a multi-layer cell sheet.
Study II examined the hypothesis that the thermo-responsive hydrogel was used as a coating on TCPS dishes and developed for harvesting living cell sheets. The obtained MSC sheets preserved the intercellular junctions and endogenous extracellular matrix and kept their cell phenotype. After injection through a needle, the fragmented MSC sheets maintained intact and retained their activity upon transferring to another growth surface, while the complete cell sheets were torn into pieces. Transplantation of fragmented MSC sheets in the skeletal muscle of a syngeneic rat model via local injection was evaluated. The transplanted MSC sheets were mainly localized at the site of injection, while the dissociated MSCs were scattered around. Additionally, there were more MSCs retained in the local skeletal muscles for the group injected with fragmented MSC sheets than that injected with dissociated MSCs. These results indicated that the fragmented cell sheets may be used as a novel therapeutic cell-carrier for intramuscular administration.
In study III, we hypothesized that the use of cell-sheet fragments, with the preservation of extracellular matrix (ECM), may significantly increase cell retention and thus improve cell therapy. Mesenchymal-stem-cell (MSC) sheet fragments with ECM were fabricated. Using a rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n ≧ 10): sham; PBS; dissociated MSCs; and MSC sheet fragments. The results obtained in the echocardiography and pressure measurements revealed a superior heart function in the MSC-sheet-fragment group compared with the dissociated-MSC group (P < 0.05). The MSC sheet fragments were able to conform and align their inherent ECM along with the interstices of the muscular tissues at the injection sites, while only a few cells were identified in the dissociated-MSC group at 12 weeks postoperatively. Additionally, transplantation of the MSC sheet fragments stimulated a significant increase in vascular density (P < 0.05) and enhanced the graft/host cell connection.
Myocardial infarction often leads to left ventricular dilation, thus impairing cardiac functions. To restore the dilated LV, a possible strategy is to replace the infarcted myocardium with bioengineered tissue grafts. The goal of tissue engineering is to repair or replace the damaged organ or tissues by delivering functional cells on supporting scaffolds to areas in need. Therefore, in study IV, a novel bioengineered tissue graft, a porous acellular bovine pericardium sandwiched with multilayered sheets of MSC, was developed for the treatment of MI. It was previously shown by our group that the acellular bovine pericardium fixed with genipin can provide a natural microenvironment for host cell migration and may be used as a tissue-engineering scaffold. We hypothesized that this newly developed tissue graft can provide the required mechanical strength to support the sandwiched multilayered sheets of MSC for tissue regeneration to restore the dilated LV and improve cardiac functions in a syngeneic rat model. The implanted samples were retrieved at 12-week postoperatively (n ≧ 10 per group at each time point) and were used for gross and histological examinations.

ABSTRACT…...………………………………………………………..I
TABLE OF CONTENT………………………………………………....III
LIST OF FIGURES…………………………………………………..VIII
LIST OF TABLES…….………………………………………..…….XII

Chapter 1.  Introduction..............................    1

Chapter 2. A Novel Living-Cell-Sheet Harvest System Composed of Thermoreversible Methylcellulose Hydrogels
2-1    Materials and Methods.................    6
2-1-1    Preparation of Aqueous MC Solutions    .........6
2-1-2    Gelation Temperatures of Aqueous MC Solutions    7
2-1-3    Preparation of the MC-Hydrogel Coated TCPS Dish    ..............................................7
2-1-4    Cell Culture..................................8
2-1-5    Detachment of Cell Sheets.....................8
2-1-6    Immunofluorescence Staining    ...................9
2-1-7    Statistical Analysis...........................9
2-2    Results and Discussion........................10
2-2-1    Gelation of Aqueous MC Solutions..............10
2-2-2    Stability of the Coated MC Hydrogel...........15
2-2-3    Cell Culture on the Surface of the MC Hydrogel    ..............................................19
2-2-4    Detachment of Cell Sheets.....................21
2-2-5    Applications of the Developed Technique.......24
2-3    Conclusions...................................26

Chapter 3. Construction and characterization of fragmented mesenchymal-stem-cell sheets with a uniform size for intramuscular injection
3-1    Materials and Methods..........................27
3-1-1    Preparation of Aqueous MC......................27
3-1-2    Preparation of the Collagen/MC-coated TCPS Dish    ...............................................28
3-1-3    Culture of MSCs on the Collagen/ MC-coated TCPS Dish    ...............................................29
3-1-4    Construction and Characterization of Fragmented Sheets of MSCs..........................................30
3-1-5    Animal Study...................................30
3-1-6    Morphometry....................................30
3-1-7    Statistical Analysis...........................32
3-2    Results and Discussion.........................32
3-2-1    Characterization of Aqueous MC blended with PBS    ...............................................32
3-2-2    Culture of MSCs on the Collagen/MC-coated Surface    ...............................................35
3-2-3    Construction and Characterization of Fragmented MSC Sheets..............................................27
3-2-4    Animal study...................................42
3-3    Conclusions.....................................44

Chapter 4.  Direct Intramyocardial Injection of Mesenchymal Stem-Cell Sheet Fragments Improves Cardiac Functions after Infarction
4-1    Materials and Methods...........................45
4-1-1    Preparation of the Cell-Sheet Culture System....45
4-1-2    Characterization of MSC Sheets..................46
4-1-3    Construction and Characterization of MSC Sheet Fragments    ................................................47
4-1-4    Animal Study....................................48
4-1-5    LV Function Assessment by Echocardiography......49
4-1-6    LV Catheterization    ..............................50
4-1-7    Histological Examinations.......................50
4-1-8    Statistical Analysis............................51
4-2    Results.........................................42
4-2-1    Characteristics of MSCs in Cell Sheets..........52
4-2-2    Characterization of MSC Sheet Fragments.........52
4-2-3    Animal Study....................................56
4-2-4    LV Function Assessment by Echocardiography and    Catheterization..........................................56
4-2-5    Morphological and Histological Findings.........56
4-3    Discussion......................................63
4-4    Conclusions.....................................66

Chapter 5.   Porous Tissue Grafts Sandwiched with Multilayered Mesenchymal Stem Cell Sheets Induced Neovascularization and Tissue Regeneration for Cardiac Repair
5-1    Materials and Methods...........................67
5-1-1    Production of Multilayered Cell Sheets..........67
5-1-2    Preparation of Porous Tissue Scaffolds..........68
5-1-3    Porous Tissue Grafts Sandwiched with Multilayered Cell Sheets..............................................69
5-1-4    Animal Study....................................69
5-1-5    LV Function Assessment by Echocardiography......70
5-1-6    LV Catheterization..............................71
5-1-7    Histological Examinations.......................71
5-1-8    Statistical Analysis............................72
5-2    Results.........................................73
5-2-1    Characteristics of Porous Tissue Grafts Sandwiched with Multilayered Sheets of MSC...............73
5-2-2    Animal Study....................................74
5-2-3    LV Function Assessment..........................74
5-2-4    Gross Examination...............................75
5-2-5    Histological Findings...........................75
5-3    Discussion......................................82
5-4    Conclusions.....................................86

References...............................................87
著作目錄.................................................98
作者簡歷................................................103

                                

1. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infracted myocardium. Nature. 2001;410:701-705.
2. Anversa P, Nadal-Ginard B. Myocyte renewal and ventricular remodelling. Nature. 2002;415:240-243.
3. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143-147.
4. Davani S, Marandin A, Mersin N, et al. Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model. Circulation. 2003;108:253-2588.
5. Saito T, Kuang JQ, Lin CC, et al. Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovasc Surg. 2003;126:114-123.
6. Tomita S, Mickle DA, Weisel RD, et al. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg. 2002;123:1132-1140.
7. Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001;107:1395-1402.
8. Freshney RI, eds. Culture of animal cells: A manual of basic technique. 3rd ed. Wiley-Liss. New York; 1994.
9. Memon IA, Sawa Y, Fukushima N, et al. Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets. J Thorac Cardiovasc Surg. 2005;130:1333-1341.
10. Okano T, Yamada N, Sakai H, et al. A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide). J Biomed Mater Res 1993;27:1243-1251.
11. Okano T, Yamada N, Okuhara M, et al. Mechanism of cell detachment from temperature-modulated, hydrophilic-hydrophobic polymer surfaces. Biomaterials 1995;16:297-303.
12. Shimizu T, Yamato M, Kikuchi A, et al. Cell sheet engineering for myocardial tissue reconstruction Biomaterials. 2003;24:2309-2316.
13. Yang J, Yamato M, Kohno C, et al. Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials. 2005;26:6415-6422.
14. Kim YS, Lim JY, Donahue HJ, et al. Thermoresponsive terpolymeric films applicable for osteoblastic cell growth and noninvasive cell sheet harvesting. Tissue Eng. 2005;11:30-40.
15. Ott E, Spurlin HM, Grafflin MW. Cellulose and Cellulose Derivatives; Interscience Publishers, Inc.: New York, 1963; 5, 930.
16. Zheng P, Li L, Hu X, et al. Sol-gel transition of methylcellulose in phosphate buffer saline solution. Polym. Sci., Part B: Polym. Phys. 2004;42:1849-1860.
17. Ron ES, Bromberg LE. Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv. Drug Deliv Rev. 1998;31:197-221.
18. Wolff AH, Oehme FW. Carcinogenic chemicals in food as an environmental health issue. J Am Vet Med Assoc. 1974;164:623-629.
19. Liu SQ, Yang YY, Liu XM, et al. Preparation and characterization of temperature-sensitive poly(N-isopropylacrylamide)-b-poly(D,L-lactide) microspheres for protein delivery. Biomacromolecules 2003;4:1784-1793.
20. Gupta KC, Khandekar K. Temperature-responsive cellulose by ceric(IV) ion-initiated graft copolymerization of N-isopropylacrylamide. Biomacromolecules 2003;4:758-765.
21. Benns JM, Choi JS, Mahato RI, et al. pH-sensitive cationic polymer gene delivery vehicle: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer. Bioconjug. Chem. 2000;11:637-645.
22. Ramkissoon-Ganorkar C, Liu F, Baudys M, et al. Modulating insulin-release profile from pH/thermosensitive polymeric beads through polymer molecular weight. J. Control. Release 1999;59:287-298.
23. Brahim S, Narinesingh D, Guiseppi-Elie A. Release characteristics of novel pH-sensitive p(HEMA-DMAEMA) hydrogels containing 3-(trimethoxy-silyl) propyl methacrylate. Biomacromolecules 2003;4: 1224-1231.
24. Ju HK, Kim SY, Lee YM. pH/temperature-responsive behaviors of semi-IPN and comb-type graft hydrogels composed of alginate and poly(N-isopropylacrylamide). Polymer. 2001;42:6851-6857.
25. Zhang Y, Wang S, Eghtedari M, et al. Inverted-colloidal-crystal hydrogel matrices as three-dimensional cell scaffolds. Adv Funct Mater. 2005;15:725-731.
26. Nakayama A, Kakugo JP, Gong Y, et al. High Mechanical Strength Double-Network Hydrogel with Bacterial Cellulose. Adv Funct Mater. 2004;14:1124-1128
27. Li L, Shan H, Yue CY, et al. Thermally Induced Association and Dissociation of Methylcellulose in Aqueous Solutions. Langmuir. 2002;18:7291-7298.
28. Xu Y, Li L, Zheng P, Lam YC, et al. Controllable gelation of methylcellulose by a salt mixture. Langmuir. 2004;20:6134-6138.
29. Lee J W, Hua FJ, Lee DS. Thermoreversible gelation of biodegradable poly(epsilon-caprolactone) and poly(ethylene glycol) multiblock copolymers in aqueous solutions. J. Control. Release 2001;73:315-327.
30. Jeong B, Kim SW, Bae YH. Thermosensitive sol-gel reversible hydrogels. Adv Drug Deliv Rev. 2002 ;54:37-51.
31. Tate MC, Shear DA, Hoffman SW, et al. Biocompatibility of methylcellulose-based constructs designed for intracerebral gelation following experimental traumatic brain injury. Biomaterials. 2001;22: 1113-1123.
32. Liang HF, Hong MH, Ho RM, et al. Novel method using a temperature-sensitive polymer (methylcellulose) to thermally gel aqueous alginate as a pH-sensitive hydrogel. Biomacromolecules 2004;5: 1917-1925.
33. Chen CH, Chang Y, Wang CC, et al. Construction and characterization of fragmented mesenchymal-stem-cell sheets for intramuscular injection. Biomaterials. 2007;28:4643-4651.
34. Fukuda K. Progress in myocardial regeneration and cell transplantation. Circ J. 2005;69:1431-1446.
35. Teng CJ, Luo J, Chiu RC, et al. Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: Implications for cellular cardiomyoplasty. J Thorac Cardiovasc Surg. 2006;132:628-632.
36. Kochupura PV, Azeloglu EU, Kelly DJ, et al. Tissue-engineered myocardial patch derived from extracellular matrix provides regional mechanical function. Circulation. 2005;112(9 Suppl):I-144-I-149.
37. Zimmermann WH, Melnychenko I, Wasmeier G, et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med. 2006;12:452-458.
38. Li RK, Jia ZQ, Weisel RD, et al. Survival and function of bioengineered cardiac grafts. Circulation. 1999;100(19 Suppl):II-63-II-69.
39. Robinson KA, Li J, Mathison M, et al. Extracellular matrix scaffold for cardiac repair. Circulation. 2005;112(9 Suppl):I-135-I-143.
40. Leor J, Amsalem Y, Cohen S. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacol Ther. 2005;105:151-163.
41. Carrier RL, Rupnick M, Langer R, et al. Perfusion improves tissue architecture of engineered cardiac muscle. Tissue Eng. 2002;8:175-188.
42. Christman KL, Lee RJ. Biomaterials for the treatment of myocardial infarction. J Am Coll Cardiol. 2006;48:907-913.
43. Solchaga LA, Tognana E, Penick K, et al. A rapid seeding technique for the assembly of large cell/scaffold composite constructs. Tissue Eng. 2006;12:1851-1863.
44. Chang Y, Chen SC, Wei HJ, et al. Tissue regeneration observed in a porous acellular bovine pericardium used to repair a myocardial defect in the right ventricle of a rat model. J Thorac Cardiovasc Surg. 2005;130:705-711.
45. Wei HJ, Chen SC, Chang Y, et al. Porous acellular bovine pericardia seeded with mesenchymal stem cells as a patch to repair a myocardial defect in a syngeneic rat model. Biomaterials. 2006;27:5409-5419.
46. Chang Y, Lai PH, Wei HJ, et al. Tissue regeneration observed in a basic fibroblast growth factor-loaded porous acellular bovine pericardium populated with mesenchymal stem cells. J Thorac Cardiovasc Surg. 2007;134:65-73.
47. Chen CN, Sung HW, Liang HF, et al. Feasibility study using a natural compound (reuterin) produced by Lactobacillus reuteri in sterilizing and crosslinking biological tissues. J. Biomed. Mater. Res. 2002;61:360-369.
48. Kundu PP, Kundu M. Effect of salts and surfactant and their doses on the gelation of extremely dilute solutions of methyl cellulose. Polymer. 2001;42:2015-2020.
49. Heymann E. Trans Faraday Soc. 1935;35:846-864.
50. Haque A, Morris ER. Thermogelation of methylcellulose. Part I: molecular structures and processes. Carbohydr Polym. 1993;22:161-173.
51. Sarkar N, Walker LC. Hydration-dehydration properties of methylcellulose and hydroxypropylmethylcellulose. Carbohydr Polym. 1995;27:177-185.
52. Mitchell K, James L. Ford DJ, et al. The influence of additives on the cloud point, disintegration and dissolution of hydroxypropylmethylcellulose gels and matrix tablets. Int J Pharm. 1990;66:233-242.
53. Alexandridis P, Holzwarth JF. Differential Scanning Calorimetry Investigation of the Effect of Salts on Aqueous Solution Properties of an Amphiphilic Block Copolymer (Poloxamer). Langmuir. 1997;13:6074-6082.Grignon, J.; Scallan, A. M. J. Appl. Polym. Sci. 1980, 25, 2829.
54. Proctor, H. R. J. Chem. Soc. 1914, 105, 313.
55. Freshney RI, Culture of Animal Cells: A Manual of Basic Technique; Wiley-Liss: New York, 1994.
56. Pederson AW, Ruberti JW, Messersmith PB. Thermal assembly of a biomimetic mineral/collagen composite. Biomaterials. 2003;24:4881-4890.
57. Gelman, R. A.; Williams, B. R.; Piez, K. A. J. Biol. Chem. 1979, 254, 180.
58. Neff JA, Tresco PA, Caldwell KD. Surface modification for controlled studies of cell-ligand interactions. Biomaterials. 1999;20:2377-2393.
59. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of The Cell; Garland Science: New York, 2002.
60. Wilhelm SM, Eisen AZ, Teter M, et al. Human fibroblast collagenase: glycosylation and tissue-specific levels of enzyme synthesis. Proc. Natl. Acad. Sci. U. S. A. 1986;83:3756-3760.
61. Kaihara S, Borenstein J, Koka R, et al. Silicon micromachining to tissue engineer branched vascular channels for liver fabrication. Tissue Eng. 2000;6:105-117.
62. Ogawa K, Ochoa ER, Borenstein J, et al. The generation of functionally differentiated, three-dimensional hepatic tissue from two-dimensional sheets of progenitor small hepatocytes and nonparenchymal cells. Transplantation. 2004;77:1783-1789.
63. Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 1995;18:1417-1426.
64. Tomita S, Li RK, Weisel RD, et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 1999;100:II247-256.
65. Davis ME, Hsieh PC, Takahashi T, et al. Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction. Proc Natl Acad Sci U S A. 2006;103:8155-8160.
66. Bao F, Chen Y, Dekaban GA, et al. Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats. J Neurochem 2004;88:1335-1344.
67. Kundu PP, Kundu M. Effect of salts and surfactant and their doses on the gelation of extremely dilute solutions of methyl cellulose. Polymer 2001;42: 2015-2020.
68. Haque A, Morris ER. Thermogelatin of methylcellulose. Part I: molecular-structures and processes. Carbohyd Polym 1993;22:161-173.
69. Haque A, Richardson RK, Morris ER. Thermogelatin of methylcellulose. Part II: effect of hydroxypropyl substituents. Carbohyd Polym 1993;22:175-186.
70. Chen CH, Tsai CC, Chen W, et al. Novel living cell sheet harvest system composed of thermoreversible methylcellulose hydrogels. Biomacromolecules 2006;7:736-743.
71. Pederson AW, Ruberti JW, Messersmith PB. Thermal assembly of a biomimetic mineral/collagen composite. Biomaterials 2003;24:4881-4890.
72. Gelman RA, Williams BR, Piez KA. Collagen fibril formation. Evidence for a multistep process. J Biol Chem 1979;254:180-186.
73. Neff JA, Tresco PA, Caldwell KD. Surface modification for controlled studies of cell-ligand interactions. Biomaterials 1999;20:2377-2393.
74. Vasioukhin V, Fuchs E. Actin dynamics and cell-cell adhesion in epithelia. Curr Opin Cell Biol 2001;13:76-84.
75. He J, Baum LG. Galectin interactions with extracellular matrix and effects on cellular function. Methods Enzymol 2006;417:247-256.
76. Cabot PJ, Carter L, Gaiddon C, et al. Immune cell-derived β-endorphin: Production, release, and control of inflammatory pain in rats. J Clin Invest 1997;100:142-148.
77. Teng CJ, Luo J, Chiu RC, et al. Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: Implications for cellular cardiomyoplasty. J Thorac Cardiovasc Surg 2006;132:628-632.
78. Nagaya N, Fujii T, Iwase T, et al. Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 2004;287:2670-2676.
79. Toma C, Pittenger MF, Cahill KS, et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002;105:93-98.
80. Hsieh PC, MacGillivray C, Gannon J, et al. Local controlled intramyocardial delivery of platelet-derived growth factor improves postinfarction ventricular function without pulmonary toxicity. Circulation 2006;114:637-644.
81. Dai W, Hale SL, Martin BJ, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation. 2005;112:214-223.
82. Krupnick AS, Kreisel D, Engels FH, et al. A novel small animal model of left ventricular tissue engineering. J Heart Lung Transplant. 2002;21:233-243.
83. Matsushita T, Oyamada M, Kurata H, et al. Formation of cell junctions between grafted and host cardiomyocytes at the border zone of rat myocardial infarction. Circulation. 1999;100:262-268.
84. Sottile J, Hocking DC, Swiatek PJ. Fibronectin matrix assembly enhances adhesion-dependent cell growth. J Cell Sci 1998;111:2933-2943.
85. Hsieh PC, Davis ME, Gannon J, et al. Controlled delivery of PDGF-BB for myocardial protection using injectable self-assembling peptide nanofibers. J Clin Invest 2006;116:237-248.
86. Klocke R, Tian W, Kuhlmann MT, et al. Surgical animal models of heart failure related to coronary heart disease. Cardiovasc Res 2007;74:29-38.
87. Muller-Ehmsen J, Whittaker P, Kloner RA, et al. Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. J Mol Cell Cardiol 2002;34:107-116.
88. Möllmann H, Nef HM, Kostin S,et al. Bone marrow-derived cells contribute to infarct remodeling. Cardiovasc Res 2006;71:661-671.
89. Reinecke H, Zhang M, Bartosek T, et al. Survival, integration, and differentiation of cardiomyocyte grafts: A study in normal and injured rat hearts. Circulation 1999;100:193-202.
90. Huang NF, Yu J, Sievers R, et al. Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Eng 2005;11:1860-1866.
91. Dai W, Wold LE, Dow JS, et al. Thickening of the infarcted wall by collagen injection improves left ventricular function in rats: a novel approach to preserve cardiac function after myocardial infarction. J Am Coll Cardiol 2005;46:714-719.
92. Ohnishi S, Yanagawa B, Tanaka K,et al. Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. J Mol Cell Cardiol 2007;42:88-97.
93. Martin I, Shastri VP, Padera RF, et al. Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams. J Biomed Mater Res. 2001;55:229-235.
94. Lee JM, Haberer SA, Boughner DR. The bovine pericardial xenograft: I. Effect of fixation in aldehydes without constraint on the tensile viscoelastic properties of bovine pericardium. J Biomed Mater Res. 1989;23:457-475.
95. Chen H, Ouyang W, Lawuyi B,et al. Reaction of chitosan with genipin and its fluorogenic attributes for potential microcapsule membrane characterization. J Biomed Mater Res. 2005;75:917-927.
96. Matsubayashi K, Fedak PW, Mickle DA,et al. Improved left ventricular aneurysm repair with bioengineered vascular smooth muscle grafts. Circulation. 2003;108(Suppl 1):II-219-II-225.
97. Kim BO, Tian H, Prasongsukarn K, et al. Cell transplantation improves ventricular function after a myocardial infarction: A preclinical study of human unrestricted somatic stem cells in a porcine model. Circulation. 2005;112(9 Suppl):I-96-I-104.
98. Huang NF, Yu J, Sievers R, et al. Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Eng. 2005;11:1860-1866.
99. Park TG. Perfusion culture of hepatocytes within galactose-derivatized biodegradable poly(lactide-co-glycolide) scaffolds prepared by gas foaming of effervescent salts. J Biomed Mater Res. 2002;59:127-135.
100. Weinstein R, Riordan MA, Wenc K, et al. Dual role of fibronectin in hematopoietic differentiation. Blood. 1989;73:111-116.
101. Mercurius KW, Morla AO. Inhibition of vascular smooth muscle cell growth by inhibition of fibronectin matrix assembly. Circ Res. 1998;82:548-556.
102. Ozawa T, Mickle DA, Weisel RD, et al. Histologic changes of nonbiodegradable and biodegradable biomaterials used to repair right ventricular heart defects in rats. J Thorac Cardiovasc Surg. 2002;124:1157-1164.
103. Schneider PA, Hanson SR, Price TM, et al. Confluent durable endothelialization of endarterectomized baboon aorta by early attachment of cultured endothelial cells. J Vasc Surg. 1990;11:365-372.
104. Leak LV, Ferrans VJ, Cohen SR, et al. Animal model of acute pericarditis and its progression to pericardial fibrosis and adhesions: Ultrastructural studies. Am J Anat. 1987;180:373-390.
105. Whitaker D, Papadimitriou JM, Walters MN. The mesothelium and its reactions: A review. Crit Rev Toxicol. 1982;10:81-144.
106. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7:430-436.
107. Kinnaird T, Stabile E, Burnett MS, et al. Bone marrow-derived cells for enhancing collateral development mechanisms, animal data, and initial clinical experiences. Circ Res. 2004;95:354-363.
108. Boyle AJ, Schulman SP, Hare JM, et al. Is stem cell therapy ready for patients? Stem cell therapy for cardiac repair. Ready for the next step. Circulation. 2006 25;114:339-352.
109. Murry CE, Reinecke H, Pabon LM. Regeneration gaps: Observations on stem cells and cardiac repair. J Am Coll Cardiol. 2006;47:1777-1785.

全文公開日期本全文未授權公開 (校內網路)
全文公開日期本全文未授權公開 (校外網路)

簡易檢索 / 詳目顯示

相關論文