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研究生:蔣恩榮
研究生(外文):En-Rung Chiang
論文名稱:低氧異體幹細胞移植治療退化性膝關節炎之兔子動物模型之機轉探討
論文名稱(外文):Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits
指導教授:洪士杰
指導教授(外文):Shih-Chieh Hung
學位類別:博士
校院名稱:國立陽明大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:36
中文關鍵詞:間葉幹細胞前十字韌帶截斷玻尿酸退化性膝關節炎SPIOTGF beta
外文關鍵詞:Mesenchymal stem cellAnterior cruciate ligament transectionHyaluronic acidOsteoarthritisSuperparamagnetic iron oxide nanoparticlesTransforming growth factor beta
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  • 點閱點閱:275
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  • 下載下載:10
  • 收藏至我的研究室書目清單書目收藏:0
臨床上,關節退化造成的關節軟骨的缺損是一個棘手的問題。而使用間葉幹細胞(MSC)來治療此種軟骨的缺損在近年來被提出。此外,許多先前的研究結果發現在低氧環境培養下,可以改變間葉幹細胞的特性,同時也可以增進間葉幹細胞的很多效能。在此,我們的研究目的即是要了解在兔子前十字韌帶截斷所產生的膝蓋退化性關節炎中,使用異體低氧間葉幹細胞注射的治療效果,以及其可能的治療機轉。首先,從骨髓分離出異體之低氧間葉幹細胞,並培養於低氧環境 (1% O2). 在兔子雙膝前十字韌帶截斷八週後,將幹細胞懸浮於玻尿酸(hyaluronic acid (HA))中並注射至膝關節中,對側的膝蓋則只注射玻尿酸.此外,另有未接受截斷手術以及只接受截斷手術而未接受注射的膝蓋當作控制組。在六週及十二週後,將膝蓋的組織做免疫染色切片分析及基因分析。我們發現,在細胞注射六週及十二週後,有細胞治療的膝蓋顯示出明顯較少的軟骨表面磨損及缺損,也有明顯較高的組織評分。並且也可以在關節不同的組織中發現注入的幹細胞,顯示注射後,幹細胞可以存活並生長達十二週之久。此外,關節組織的基因分析也發現細胞治療對於一些關節炎相關的基因表現也是有利的。因此,我們認為將低氧培養之異體骨髓間葉幹細胞應用於軟骨修復是安全且可行的,並且此種細胞注射具有降低退化性關節炎生成的療效。
Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects and mechanism of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. Additionally, several osteoarthritic-related gene expression levels in the cartilage samples were analyzed by q-PCR to further clarify the potential regenerative mechanism of the hypoxic MSCs. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Engraftment of allogenic MSCs were also evident in surface cartilage. Furthermore, cell injection had demonstrated some favorable effects on the expression level of the osteoarthritic-related genes. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.
Contents…………………………………………………………………………........i
English Abstract………………………………………………………………….......ii
Chinese Abstract.…......……………………………………………………….……iii
List of Abbreviations………………………………………………………………iv
1. Introduction…………..…………………………………….…………………......1
2. Materials and Methods……………………………………………………….…..3
3. Results……………………………………………………………………………11
4. Discussion………………………………………………………………….…….15
5. Conclusion.………………………………………………………………………20
6. Reference……………………………………………………………………..…21
7. Figures………………………………………………………………….…..25
8. Publications…………………………………………………………………….36
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