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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳信志(Shinn-Chih Wu) | |
| dc.contributor.author | Xuan-Chun Su | en |
| dc.contributor.author | 蘇暄淳 | zh_TW |
| dc.date.accessioned | 2022-11-25T07:29:02Z | - |
| dc.date.available | 2025-01-25 | |
| dc.date.copyright | 2022-02-18 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-01-25 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82307 | - |
| dc.description.abstract | "組織工程作為臨床醫學上新興的骨骼損傷治療方式，改善了無論是自體、異體、異種和人工骨移植等治療的限制。過去已經有許多研究證實以細胞、支架和生長因子共同移植之組織工程於骨修復上有其功效。其中間葉幹細胞（mesenchymal stem cell, MSC）是組織工程研究中的最廣泛被運用的細胞種類。隨著對於間葉幹細胞的研究愈加深入，許多研究認為間葉幹細胞是透過旁分泌作用來調控組織修復，因此無需細胞的治療方式（cell-free therapy）逐漸成為組織工程研究的趨勢。而培養過間葉幹細胞之培養液，被稱為間葉幹細胞條件培養液（MSCs derived-conditioned medium, MSC-CM），其中含有間葉幹細胞分泌的所有因子，被認為是一種可取代細胞的組織工程材料。 明膠止血綿作為臨床醫學中常見的生醫材料，具有良好的生物相容性和生物降解性。在我們先前的研究中，已經證實綠螢光豬的間葉幹細胞搭配明膠止血棉能有效的治療豬的頭骨缺損；進一步，我們希望於大鼠頭骨缺損模型中測試載有條件培養液之明膠止血綿是否同樣具修復效果。 在體外試驗中，我們發現條件培養液能調控間葉幹細胞成骨相關基因的表現，其中包含RUNX2和OCN都有較高的表現量，而透過Transwell的遷移測試，我們則發現條件培養液對於間葉幹細胞有招募的效果。另外一方面，在螢光顯微鏡觀察、CCK-8測定和鹼性磷酸酶的染色結果中，我們證實了明膠止血棉確實是有助於間葉幹細胞的增生和分化。在體內試驗中，空白組作為對照，其餘分別以新鮮培養液（FM group）、條件培養液（CM group）、5×10^4個綠螢光豬間葉幹細胞（MSC group）搭配明膠止血綿移植在大鼠頭骨缺損模型中進行6週和10週的修復測試。在微電腦斷層掃描得結果中，無論是在第6週或第10週，與對照組和FM組相比，CM和MSC組新生成骨頭的面積都是顯著較大的；另外有趣的是，我們發現CM組開始進行骨修復的時間早於MSC組。 綜上所述，在體外試驗中，我們知道條件培養液有招募間葉幹細胞及誘導骨分化的作用，而明膠止血綿有很好的生物相容性讓間葉幹細胞能在其中增殖、分化。在體內則驗證了明膠止血綿搭配條件培養液對骨再生同樣具有治療功效。這些結果顯示條件培養液透過調控宿主間葉幹細胞能取代外源性間葉幹細胞在骨修復組織工程中的作用；而在無需細胞的治療方式中，明膠止血綿搭配條件培養液的治療在未來臨床醫學上的應用是備受期待的。 " | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T07:29:02Z (GMT). No. of bitstreams: 1 U0001-2501202213165100.pdf: 3347964 bytes, checksum: 9229c526a3a7d716af8ad7b48076b79c (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | "CONTENTS 致謝 I 中文摘要 II Abstract IV CONTENTS VI LIST OF FIGURES IX LIST OF TABLES X Part 1- Introduction 1 Part 2- Background 2 2.1 Bone 2 2.1.1 Four types of cells in bone 2 2.1.2 Bone structure 4 2.1.3 Bone matrix 8 2.1.4 Bone ossification 8 2.1.5 Therapeutic difficulty in bone 9 2.2 Tissue engineering 10 2.2.1 Bone tissue engineering 11 2.2.2 Cell 11 2.2.3 Scaffold 12 2.2.4 Regulatory signals 14 2.2.5 Exogenic cell-free therapy 14 Part 3- Research motivation 16 Part 4- Experimental design with material and method 20 4.1 The biological regulation of MSC-CM on MSCs in vitro. 20 4.1.1 Culture of EGFP-pMSCs 21 4.1.2 Preparation of MSC-CM 21 4.1.3 RNA extraction 22 4.1.4 Reverse transcription reaction 23 4.1.5 Quantitative polymerase chain reaction, QPCR 23 4.1.6 Migration assay 24 4.1.7 Statistical analysis 25 4.2 In vitro viability and osteogenesis of EGFP-pMSCs loaded on hemostatic gelatin sponge 26 4.2.1 Prepare the construct of scaffold 27 4.2.2 Proliferation test of EGFP-pMSCs on scaffolds 27 4.2.3 Osteogenic differentiation test of EGFP-pMSCs on scaffolds 27 4.2.4 Statistical analysis 28 4.3 Osteogenic regeneration of MSC-CM with hemostatic gelatin sponge transplanted into rat calvarial bone defect 29 4.2.5 Prepare the construct of scaffold 30 4.2.6 Rat calvarial bone defect model 30 4.2.7 Radiographic 30 4.2.8 Statistical analysis 31 Part 5- Results 32 5.1 In vitro regulation of MSC-CM on MSCs. 32 5.1.1 Culture of EGFP-pMSCs and RFP-pMSCs 32 5.1.2 MSC-CM up-regulates osteogenic gene expression of pMSCs 33 5.1.3 In vitro recruitment of MSCs by MSC-CM. 33 5.2 In vitro evaluation of EGFP-pMSCs loaded on hemostatic gelatin sponge 37 5.2.1 Biocompatibility of hemostatic gelatin sponge to EGFP-pMSCs 37 5.2.2 Osteoconduction of hemostatic gelatin sponge with EGFP-pMSCs 37 5.3 Osteogenic regeneration of MSC-CM with hemostatic gelatin sponge transplanted into rat calvarial bone defect 40 Part 6- Discussion 44 Part 7- Conclusion 47 Part 8- Reference 48 LIST OF FIGURES Figure 1. Four types of cells in bone remodeling. 3 Figure 2. The structure of compact bone. 6 Figure 3. The structure of trabeculae. 7 Figure 4. Triad of tissue engineering. 10 Figure 5. Schematic represent the recruitment and following osteogenic differentiation of mesenchymal stem cells (MSCs) during bone regeneration. 15 Figure 6. In vivo fluorescence quantification. 17 Figure 7. In vivo Hematoxylin and eosin staining. 18 Figure 8. In vitro experimental design for biological regulation of MSC-CM. 20 Figure 9. The flow diagram of transwells migration test (A) and parameters for quantitative analysis (B). 25 Figure 10. In vitro experimental design to evaluate the feasibility of hemostatic gelatin sponge to carry EGFP-pMSCs. 26 Figure 11. In vivo experimental design for rat calvarial bone defect model. 29 Figure 12. Fluorescence expression of EGFP-pMSCs and RFP-pMSCs in the dishes. 32 Figure 13. Effect of MSC-CM on EGFP-pMSC gene expression. 34 Figure 14. Effect of MSC-CM on the migration of EGFP-pMSCs. 35 Figure 15. EGFP-pMSCs grew and proliferated in hemostatic gelatin sponge. 38 Figure 16. Osteo-differentiation of EGFP-pMSCs in hemostatic gelatin sponge. 39 Figure 17. Establishment of rat calvarial bone defect model. 41 Figure 18. Micro-CT image of bone regeneration after hemostatic gelatin sponges with FM/CM/ EGFP-pMSC were implanted into rat calvarial bone defect. 42 Figure 19. Quantitation of bone regenerative area after hemostatic gelatin sponges with FM/CM/EGFP-pMSCs were implanted into rat calvarial bone defect. 43 LIST OF TABLES Table 1. Bone classifications 5 Table 2. Primer used in the quantitative polymerase chain reaction 24 Table 3. Composition of quantitative polymerase chain reaction 24 " | |
| dc.language.iso | en | |
| dc.subject | 頭骨缺損治療 | zh_TW |
| dc.subject | 間葉幹細胞 | zh_TW |
| dc.subject | 骨修復組織工程 | zh_TW |
| dc.subject | 條件培養液 | zh_TW |
| dc.subject | 無需細胞的治療方式 | zh_TW |
| dc.subject | conditioned medium | en |
| dc.subject | cell-free therapy | en |
| dc.subject | mesenchymal stem cell | en |
| dc.subject | bone tissue engineering | en |
| dc.subject | calvarial bone defect | en |
| dc.title | 以間葉幹細胞條件培養液搭配明膠止血棉用於治療大鼠頭骨缺損 | zh_TW |
| dc.title | Bone regeneration of mesenchymal stem cell-conditioned medium loaded hemostatic gelatin sponge on rat calvarial defect | en |
| dc.date.schoolyear | 110-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳銘正(Tung-Chieh Chen),賴伯亮(Ting-Ting Hwang),謝明凱(Shao-Yun Fang) | |
| dc.subject.keyword | 間葉幹細胞,骨修復組織工程,條件培養液,無需細胞的治療方式,頭骨缺損治療, | zh_TW |
| dc.subject.keyword | mesenchymal stem cell,bone tissue engineering,conditioned medium,cell-free therapy,calvarial bone defect, | en |
| dc.relation.page | 55 | |
| dc.identifier.doi | 10.6342/NTU202200196 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2022-01-26 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 動物科學技術學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-01-25 | - |
| 顯示於系所單位： | 動物科學技術學系 | |
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