博碩士論文 101324010 詳細資訊



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姓名 吳孟學(Meng-hsueh Wu)  查詢紙本館藏   畢業系所 化學工程與材料工程學系
論文名稱 人類脂肪幹細胞培養在具有細胞外基質接枝的水凝膠上之多能性與分化能力研究
(Pluripotency and Differentiation of Human Adipose-derived Stem Cells Cultured on ECM-grafted Hydrogels Having Different Elasticity)
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摘要(中) 人類脂肪衍生幹細胞可以經由細胞培養皿來純化,並且顯示具有分化多支鏈的能力。在過去幾十年裡，某些細胞外基質常被塗佈於二維或是三維的幹細胞培養材料上,例如: 膠原蛋白、層黏蛋白質、纖維連接蛋白、玻璃連黏蛋白質以及幹細胞的分化及生長都是常被研究的。然而這些蛋白大多數是由動物衍生出來的所以如果用這些單白質來培養幹細胞，接下來如果要應用於臨床試驗會有異種污染的問題，加上這些蛋白質價格並不便宜。為了實現我們的最終負擔得起的，個性化的再生醫學的目的，臨床上安全和經濟的方式增殖的幹細胞是絕對必要的，同時保持其多能性，以及引導幹細胞譜系規格，而無需使用化學誘導。這裡我研究多能性和人類脂肪衍生幹細胞的分化能力培養於聚（乙烯醇共衣康酸），PVA-IA，水凝膠接枝某些細胞外基質（膠原蛋白第一型，纖連蛋白和寡玻連蛋白）。PVA-IA水凝膠的軟硬度可以透過6小時到48小時的交聯時間加以控制，藉由戊二醛溶液，生成的彈性從2.2千帕至3.7千帕的儲能模量，從E計算對應軟硬度為6.6千帕至11.1千帕的彈性模量= 3G′[生物材料29（2008）2757]。
我們發現人類脂肪衍生幹細胞培養於PVA-IA接枝纖連蛋白及寡玻連蛋白於相對較軟的基材可以維持幹細胞的多能性但是於細胞培養聚苯乙烯的培養皿上卻沒有這個表現，從螢光染色的結果可以發現於我們改質過後的培養皿上有很好的表現但是於細胞培養聚苯乙烯的培養皿卻沒有什麼表現，在成骨分化的分析上
細胞培養聚苯乙烯的培養皿比分化表現優於我們改質過後的培養皿。
摘要(英) Stem cells purified from human adipose tissue (hADSCs) via serial culture of stromal vascular fraction (SVF) on tissue culture plates show multilineage differentiation ability in vitro. In the past decades, extracellular matrices (ECMs) such as collagen, fibronectin, vitronectin, and laminin were used as coating or self-standing materials on 2D culture and 3D culture of stem cells, and the differentiation and proliferation ability of stem cells (e.g., ADSCs or bone marrow-derived mesenchymal stem cells) were investigated. However, the origin of these ECMs are mainly animal-derived or human recombinant, and, therefore, it is not suitable to use them for clinical applications due to xeno-origin contamination and high cost of ECMs. On the other hand, it has been shown that physical environmental factors, such as matrix elasticity, and small functional groups including oligopeptides can have significant effect in determining stem cell fate. To achieve our ultimate goal of affordable, personalized regenerative medicine, clinically safe and economical ways to proliferate stem cells are absolutely essential while maintaining their pluripotency as well as directing stem cell lineage specification without the use of induction chemicals.
Here I investigated pluripotency and differentiation ability of hADSCs cultured on poly(vinylalcohol-co-itaconic acid), PVA-IA, hydrogels grafted with several ECMs (collagen type I, Fibronectin, and oligo-vitronectin [VN]). The stiffness of PVA-IA hydrogels can be controlled by the crosslinking time from 6 hr to 48 hr in glutaraldehyde solution, which generates the elasticity from a 2.2 kPa to 3.7 kPa storage modulus corresponding 6.6 kPa to 11.1 kPa elastic modulus from calculation of E=3G’ [Biomaterials 29 (2008) 2757].
Primary hADSCs were found to maintain their pluripotency on relatively soft hydrogels grafted with Fibronectin and oligopeptide derived from Vitronectin (KGGPQVTRGDVFTMP) from pluripotent gene expression (Nanog, Sox2, Oct4, and klf4) but not on TCPS. From the immunostaining data showed that hADSCs on ECM-grafted PVA-IA films have higher expression of pluripotent proteins than those on TCPS in expansion medium. In the osteogenic differentiation analysis, hADSCs on TCPS have higher differentiation ratio than those on ECM-grafted PVA-IA films after 21 days culture in ostogenic medium.
關鍵字(中) ★ 人類脂肪衍生幹細胞
★ 彈性
★ 間葉幹細胞		 關鍵字(英) ★ human adipose derived stem cell
★ elasticity
論文目次 Index of contents
Chapter 1. Introduction 1
1.1 Stem cells 1
1.2 Embryonic stem cells (ESCs) 1
1.2.1 Induced pluripotent stem cells (iPSCs) 2
1.2.2 Hematopoietic stem cells (HSCs) 3
1.2.3 Mesenchymal stem cells (MSCs) 3
1.3 Adipose-derived stem cells 4
1.4 Differentiation capacity of adipose-derived stem cells 6
Environmental factors and bioprocessing parameters that impact on hMSCs fate decision 6
1.4.2 Lineage-specific differentiation potential 10
1.4.3 Immunophenotype 13
1.4.4 Isolation of adipose-derived stem cells 14
1.4.4 Cell isolation 15
1.4.5 Membrane purification method 16
1.4.6 Fluorescence-activated cell sorting (FACS) 17
1.4.7 Magnetic-activated cell sorting (MACS) 20
1.5 ECM Immobilization on 2D dishs 22
1.6 Extracellular matrix (ECM) and nano-segment 24
1.6.1 Type and classification of artificial ECMs 25
1.7 Marker of pluripotent gene 33
1.7.1 Nanog 34
1.7.2 Octamer-binding transcription factor 4 (Oct4) 34
1.7.3 SRY (sex determining region Y)-box 2 (Sox-2) 35
1.7.4 Kruppel-like factor 4 (Klf4) 35
1.8 Marker of differentiation lineages of MSCs 36
1.8.1 Runt-related transcription factor 2 (Runx2) 36
1.8.2 SRY (sex determining region Y)-box 9 (Sox9) 37
1.8.3 Nestin 37
1.8.4 α-actin 38
Chapter 2. Materials and Methods 39
2.1 Materials 39
2.1.1 PVA-IA film 39
2.1.2 Culture medium 39
2.1.3 Supplement in culture medium 39
2.1.4 Digestion solution 40
2.1.5 ACK lysis buffer 40
2.1.6 Phosphate buffer saline solution (PBS) 40
2.1.7 ECM protein 40
2.1.8 RNA extraction 40
2.1.9 Reverse transcriptase (RT) 41
2.1.10 Real-time (qPCR) 41
2.1.11 Probe 41
2.2 Experimental method 43
2.2.1 PVA-IA film preparation 43
2.2.2 Preparation of PVA-IA coating dish grafted with ECM 44
2.2.3 Elasticity measurement of PVA-IA 45
2.2.4 XPS analysis of dish surface 45
2.2.5 10x Phosphate buffer saline (PBS) preparation 45
2.2.6 Culture medium preparation 46
2.2.7 Isolation and culture of adipose tissue-derived stromal cells 46
2.2.8 Culture and passage of ADSCs 49
2.2.9 Cell density measurement 50
2.2.10 Differentiation of adipose tissue-derived stem cells 51
2.2.11 Immunostaining 51
2.2.12 Isolation of total RNA 52
2.2.13 Reverse transcription of mRNA into cDNA 53
2.2.14 Quantitative real time polymerase chain reaction 54
Chapter 3. Results and Discussion 57
3.1 The elasticity of the PVA-IA gel 57
3.2 The XPS measurements of the PVA-IA films 60
3.3 Culture of primary hADSCs on PVA-IA hydrogel grafting collagen having different stiffness 73
3.4 ECM-grafted PVA-IA films having different elasticity guide primary hADSCs into specific lineages of early differentiation 87
3.5 Primary hADSCs culture on crosslinked PVA-IA films (6hr) grafting different ECMs 91
3.6 Different ECM-grafted PVA-IA films guide primary hADSCs into specific lineages of early differentiation 103
Chapter 4 Conclusion 108
Supplement 110
Reference 122










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Index of Figure
Figure 1-1. Differentiation potential of stem cells. (http://stemcells.nih.gov/info/scireport/pages/chapter1.aspx) 2
Figure 1-2. MSCs have an ability to differentiate into several kinds of cell types. (http://www.genetex.com/WebPage/Product/PromotionDetail.aspx?PromotionID=122) 4
Figure 1-3. Morphology of adipose-derived stem cells. 6
Figure 1-4. Environmental factors and bioprocessing parameters that impact on hPSCs fate decisions (quiescence, self-renewal, differentiation and apoptosis). The main environmental cues and examples of bioprocessing parameters controlling the fate of stem cells are depicted [32]. 7
Figure 1-5. In vitro development of osteoblast phenotype. (http://vschool.scu.edu.tw/biology/content/cytology.htm) 12
Figure 1-6. Cell source of regenerative medicine. 15
Figure 1-7. Preparation procedure of adipose tissue-derived stem cells [26]. 16
Figure 1-8. Diagram of FACS instrument. Cells have been fluorescently tagged with specific antibodies, and the cells that do not express the epitope go to the waste. (http://www.bio.davidson.edu/courses/genomics/method/FACS.html) 20
Figure 1-9. MACS purification of targeted cells after magnetic antibodies labeled. 22
Figure 2-1. The process of making PVA-IA coating dish grafted with ECM. 44
Figure 2-2. The counting grid pattern. (http://www.nexcelom.com/Products/Disposable-Hemacytometer.html) 51
Figure 3-1. The storage modulus of crosslinked PVA-IA films at different angular frequency, which was measured by Rheometer, Physica MCR 101. 58
Figure 3-2. The storage modulus of crosslinked PVA-IA films at1Hz angular frequency, which was measured by Rheometer, Physica MCR 101. 59
Figure 3-3. The storage modulus of crosslinked PVA-IA films at1Hz angular frequency, which was measured by Rheometer, Physica MCR 101. 59
Figure 3-4. The survey spectra of PVA-IA films by X-ray photoelectron spectroscopy. 62
Figure 3-5. The survey spectra of ECM-grafted PVA-IA films by X-ray photoelectron spectroscopy. 63
Figure 3-6. The elemental analysis of PVA-IA films and TCPS by X-ray photoelectron spectroscopy. 64
Figure 3-7. The elemental analysis of PVA-IA films by X-ray photoelectron spectroscopy. 65
Figure 3-8. The elemental analysis of PVA-IA films by X-ray photoelectron spectroscopy. 66
Figure 3-9. The elemental analysis of PVA-IA films by X-ray photoelectron spectroscopy. 67
Figure 3-10. The elemental analysis of ECM-grafted PVA-IA films by X-ray photoelectron spectroscopy. 68
Figure 3-11. The elemental analysis of ECM-grafted PVA-IA films by X-ray photoelectron spectroscopy. 69
Figure 3-12. The elemental analysis of ECM-grafted PVA-IA films by X-ray photoelectron spectroscopy. 70
Figure 3-14. N/C ratio of PVA-IA films, ECM-grafted PVA-IA films and TCPS. 72
Figure 3-15. The microenvironment of primary hADSCs cultured on ECM-grafted PVA-IA films. 75
Figure 3-16. Primary hADSCs culture on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa-3.2kPa). 75
Figure 3-17. The cell morphology of primary hADSCs cultured on PVA-IA grafting dishes having different elasticity (e.g., 2.2kPa ~3.2kPa) and TCPS in expansion medium at Passage 0. The bar indicates 100μm. 76
Figure 3-18. The cell morphology of primary hADSCs cultured on PVA-IA grafting dishes having different elasticity (e.g., 2.2kPa ~3.2kPa) and TCPS in expansion medium at Passage 4. The bar indicates 100μm. 78
Figure 3-19. Doubling time of primary hADSCs cultured on PVA-IA grafting dishes having different elasticity (e.g., 2.2kPa ~3.2kPa) and TCPS in expansion medium at Passage 1. 78
Figure 3-20. Doubling time of primary hADSCs cultured on PVA-IA grafting dishes having different elasticity (e.g., 2.2kPa ~3.2kPa) and TCPS in expansion medium at Passage 4. 79
Figure 3-21. Doubling time of primary hADSCs cultured on PVA-IA grafting dishes having different elasticity (e.g., 2.2kPa ~3.2kPa) and TCPS in expansion medium at Passage 1 and Passage 4. 80
Figure 3-22. The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 81
Figure 3-23. The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 81
Figure 3-24. The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 82
Figure 3-25. The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 82
Figure 3-27. The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 83
Figure 3-28. The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 84
Figure 3-29. The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 84
Figure 3-30. The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1 and Passage 4. 85
Figure 3-33. The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1 and Passage 4. 86
Figure 3-34. The expression of nerve cell gene (Nestin) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 88
Figure 3-35. The expression of smooth muscle cell gene (α-actin) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 88
Figure 3-37. The expression of osteogenic gene (Runx2) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 89
Figure 3-38. The expression of early endoderm differentiation (Sox17) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 90
Figure 3-39. The relationship between early differentiation genes of three germ layers and different elasticity of ECM-grafted PVA-IA films (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 90
Figure 3-40. Primary hADSCs culture on ECM-grafted PVA-IA-6hr (e.g., 2.2kPa) films. 92
Figure 3-41. The cell morphology of primary hADSCs culture on PVA-IA-6hr grafting dish and TCPS in expansion medium at Passage 0. The bar indicates 100 m. 93
Figure 3-42. Doubling time of primary hADSCs culture on PVA-IA grafting dish and TCPS in expansion medium at Passage 1. 93
Figure 3-43. The cell morphology of primary hADSCs culture on PVA-IA-6hr grafting dish and TCPS in expansion medium at Passage 4. The bar indicates 100 m. 94
Figure 3-44. Doubling time of primary hADSCs culture on PVA-IA grafting dish and TCPS in expansion medium at Passage 4. 95
Figure 3-45. Doubling time of primary hADSCs culture on PVA-IA grafting dishes and TCPS in expansion medium at Passage 1 and Passage 4. 96
Figure 3-46. The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 96
Figure 3-47. The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 97
Figure 3-48. The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 97
Figure 3-49. The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 98
Figure 3-50. The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 98
Figure 3-51. The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 99
Figure 3-52. The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 99
Figure 3-53. The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 100
Figure 3-54. The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 100
Figure 3-55. The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 101
Figure 3-56. The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 101
Figure 3-57. The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 102
Figure 3-58. Expression of pluripotent markers (Nanog, Sox2) in hADSCs at PVA-IA culture system in expansion medium at Passage 4. The bar indicates 100 m. 102
Figure 3-59. Expression of pluripotent markers (Oct4, SSEA4) of hADSCs at PVA-IA culture system in expansion medium at Passage 4. The bar indicates 100 m. 103
Figure 3-60. The expression of nerve cell gene (Nestin) of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA films and hES cells culture on matrigel at Passage 4. 104
Figure 3-61. The expression of smooth muscle cell gene (α-actin) of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA films and hES cells culture on matrigel at Passage 4. 105
Figure 3-62. The expression of early endoderm differentiation (Sox17) of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA film and hES cells culture on matrigel at Passage 4. 105
Figure 3-63. The relationship between early differentiation genes of three germ layers and different ECM-grafted PVA-IA films cultured in expansion medium at Passage 4. 106
Figure 3-64. The expression of osteogenic differentiation was analyzed by Alizarin Red S staining after the cells had been cultured for 21 days in osteogenic differentiation medium. The bar indicates 100 m. 106
Figure 3-65. The expression of osteogenic differentiation was analyzed by Alizarin Red S staining after the cells had been cultured for 21 days in osteogenic differentiation medium. The bar indicates 100 m. 107







Index of Table
Table 1-1. Characterization of freshly isolated human stromal vascular fractions from adipose tissue and mesenchymal stem cells 14
Table 1-2. Characteristics of common used natural polymers (ECMs) for tissue engineering (modified from Ref. [114]). 26
Table 1-3. Example of characteristics of common used synthetic polymers for tissue engineering (modified from Ref. [114]). 27
Table 1-4 Differentiation markers of MSCs into specific lineages [2]. 36
Table 2-1. Probes of pluripotent gene and different lineage gene. 41
Table 2-2. Primary antibody of immunostaining. 42
Table 2-3. Secondary antibody of immunostaining. 42
Table 2-4 Adipose tissue sample used in this study. 48
Table 2 5 Composition of RNA / primer solution in PCR reaction. 53
Table 2 6 Composition of RT reaction solution. 53
Table 2 7 Composition of qPCR reaction solution. 54
Table 2 8 qPCR step condition. 55
Table 3-1. The result of elasticity of PVA-IA film measured by Rheometer, Physica MCR 101. 60
Table 3-2. O/C ratio of PVA-IA films, ECM-grafted PVA-IA films and TCPS. 71
Table 3-3. N/C ratio of PVA-IA films, ECM-grafted PVA-IA films and TCPS. 72
Table 3-4. Doubling time of primary hADSCs cultured on PVA-IA grafting dishes having different elasticity (e.g., 2.2kPa ~3.2kPa) and TCPS in expansion medium at Passage 1. 79
Table 3-5. Doubling time of primary hADSCs culture on PVA-IA grafting dish having different elasticity (e.g., 2.2kPa ~3.2kPa) and TCPS in expansion medium at Passage 4. 80
Table 3-6. Doubling time of primary hADSCs culture on PVA-IA grafting dish and TCPS in expansion medium at Passage 1. 94
Table 3-7. Doubling time of primary hADSCs culture on PVA-IA grafting dish and TCPS in expansion medium at Passage 4. 95
Table supplement 3-1.The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 110
Table supplement 3-2.The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 110
Table supplement 3-3.The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 110
Table supplement 3-4.The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 111
Table supplement 3-5.The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 111
Table supplement 3-6.The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 111
Table supplement 3-7.The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 111
Table supplement 3-8.The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 112
Table supplement 3-9.The expression of nerve cell gene (Nestin) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 112
Table supplement 3-10.The expression of smooth muscle cell gene (α-actin) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 112
Table supplement 3-11.The expression of chondrocyte gene (Sox9) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 113
Table supplement 3-12.The expression of osteogenic gene (Runx2) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 113
Table supplement 3-13.The expression of early endoderm differentiation (Sox17) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 4. 113
Table supplement 3-14.The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 114
Table supplement 3-15.The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 114
Table supplement 3-16. The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 114
Table supplement 3-17. The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1. Normalize to Passage 1 TCPS. 114
Table supplement 3-18.The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 115
Table supplement 3-19.The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 115
Table supplement 3-20.The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 115
Table supplement 3-21.The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 4. Normalize to Passage 1 TCPS. 115
Table supplement 3-22.The expression of nerve cell gene (Nestin) of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA films and hES cells culture on matrigel at Passage 4. 116
Table supplement 3-23.The expression of smooth muscle cell gene (α-actin) of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA films and hES cells culture on matrigel at Passage 4. 116
Table supplement 3-24.The expression of early endoderm differentiation (Sox17) of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA film and hES cells culture on matrigel at Passage 4. 116
Table supplement 3-25.The expression of osteogenic differentiation was analyzed by Alizarin Red S staining after the cells had been cultured for 21 days in osteogenic differentiation medium. 116
Table supplement 3-26.The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1 and Passage 4. 117
Table supplement 3-27.The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1 and Passage 4. 117
Table supplement 3-28.The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1 and Passage 4. 118
Table supplement 3-29.The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films having different elasticity (e.g., 2.2kPa~3.2kPa) in expansion medium at Passage 1 and Passage 4. 118
Table supplement 3-30.The expression of pluripotent gene (Nanog) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 118
Table supplement 3-31.The expression of pluripotent gene (Sox2) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 119
Table supplement 3-32.The expression of pluripotent gene (Oct4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 119
Table supplement 3-33.The expression of pluripotent gene (klf4) of primary hADSCs cultured on ECM-grafted PVA-IA films and TCPS in expansion medium at Passage 1 and Passage 4. 119
Table supplement 3-34. Doubling time of primary hADSCs culture on PVA-IA grafting dishes and TCPS in expansion medium at Passage 1 and Passage 4. 120
Table supplement 3-35. Doubling time of primary hADSCs culture on PVA-IA grafting dishes and TCPS in expansion medium at Passage 1 and Passage 4. 120
Table supplement 3-36.The expression of early differentiation marker of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA films and TCPS at Passage 4. 120
Table supplement 3-37.The expression of early differentiation marker of primary hADSCs cultured in expansion medium on ECM-grafted PVA-IA films, TCPS and hES on matrigel at Passage 4. 121


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指導教授 ?口亞紺(Akon Higuchi) 審核日期 2014-6-16
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