本文選題：肌腱組織工程 + 肌腱分化　； 參考：《浙江大學(xué)》2014年博士論文

【摘要】：肌腱損傷是最常見的運(yùn)動性損傷之一,是骨科和運(yùn)動醫(yī)學(xué)中公認(rèn)的治療難題。統(tǒng)計(jì)表明,全球每年至少有3000萬的肌腱損傷病例,嚴(yán)重影響患者的生活質(zhì)量,并斷送了許多優(yōu)秀運(yùn)動員的職業(yè)生命。目前,臨床上對肌腱損傷的治療主要停留在理療、手術(shù)縫合以及移植階段,雖有一定效果,但是療效有限。肌腱修復(fù)后的組織和功能特性與正常肌腱相距甚遠(yuǎn),常伴隨有腱粘連、組織形態(tài)不佳(形成疤痕組織),力學(xué)差(最多達(dá)到40%強(qiáng)度),易二次損傷。因此,尋找肌腱再生修復(fù)新手段具有重要的臨床意義。 近年來,干細(xì)胞與組織工程技術(shù)的發(fā)展為提高肌腱等軟組織的修復(fù)質(zhì)量帶來了全新的機(jī)會,人們開始嘗試采用肌腱組織工程技術(shù)來治療和修復(fù)肌腱缺損。種子細(xì)胞是組織工程的關(guān)鍵要素之一。當(dāng)前肌腱組織工程研究中備受關(guān)注的種子細(xì)胞包括胚胎干細(xì)胞(ESCs)、間充質(zhì)干細(xì)胞(MSCs)和肌腱干細(xì)胞(TSPCs)等。然而目前研究發(fā)現(xiàn)以干細(xì)胞作為種子細(xì)胞修復(fù)后的肌腱在力學(xué)性能上與正常肌腱仍有顯著區(qū)別,在微觀結(jié)構(gòu)上表現(xiàn)為生成大量的小直徑的膠原纖維,而這些小直徑膠原纖維正是導(dǎo)致愈后肌腱力學(xué)性能低下的直接因素。這些結(jié)果表明目前的組織工程手段仍然只能部分提高肌腱的修復(fù)質(zhì)量,尚缺乏有效手段使干細(xì)胞完全分化為功能性肌腱細(xì)胞,達(dá)到肌腱完全再生。本論文立足于本研究室前期研究發(fā)現(xiàn)——胚胎干細(xì)胞可作為肌腱種子細(xì)胞,開展胚胎干細(xì)胞定向分化為MSCs后進(jìn)行肌腱組織工程研究以及尋找肌腱早期發(fā)育的重要調(diào)控因子用于促進(jìn)肌腱分化和修復(fù),最終目的為調(diào)控胚胎干細(xì)胞的肌腱分化,構(gòu)建組織工程肌腱,促進(jìn)肌腱修復(fù)和再生。 本論文研究內(nèi)容包含：第一部分是胚胎干細(xì)胞構(gòu)建組織工程肌腱用于肌腱修復(fù)的研究。通過運(yùn)用胚胎干細(xì)胞來源的間充質(zhì)干細(xì)胞(ESC-MSCs)與網(wǎng)狀-蠶絲膠原復(fù)合支架構(gòu)建組織工程肌腱,用于肌腱修復(fù)。第二部分是肌腱分化相關(guān)重要基因篩選的研究。通過發(fā)育生物學(xué)研究,我們首次將肌腱發(fā)育、成熟分為不同的階段,評估肌腱正常發(fā)育過程中的組織形態(tài)與內(nèi)在分子信號改變,結(jié)合生物芯片數(shù)據(jù)進(jìn)行篩選,發(fā)現(xiàn)fos基因在肌腱階段性分化過程中發(fā)揮著重要調(diào)控作用,并進(jìn)一步通過基因過表達(dá)和基因沉默實(shí)驗(yàn)得到驗(yàn)證。第三部分是fos基因用于胚胎干細(xì)胞向早期肌腱分化的研究。通過在胚胎干細(xì)胞來源的間充質(zhì)干細(xì)胞中過表達(dá)fos基因,促進(jìn)細(xì)胞向早期肌腱分化。 本研究的成果和發(fā)現(xiàn)為利用胚胎干細(xì)胞修復(fù)再生肌腱提供了新的實(shí)驗(yàn)依據(jù)和分化知識,并根據(jù)肌腱發(fā)育提出肌腱階段性分化作為肌腱組織工程誘導(dǎo)的手段,為未來肌腱損傷治療帶來新的種子細(xì)胞和技術(shù)手段。
[Abstract]:Tendon injury is one of the most common sports injuries and is recognized as a difficult problem in orthopedics and sports medicine.Statistics show that there are at least 30 million cases of tendon injury every year in the world, which seriously affects the quality of life of patients and results in the loss of professional life of many excellent athletes.At present, the clinical treatment of tendon injury mainly stays at the stage of physiotherapy, surgical suture and transplantation, although it has certain effect, but the curative effect is limited.The tissue and functional characteristics of tendon repair are far from normal tendon, often accompanied by tendon adhesion, poor tissue morphology (formation of scar tissue, mechanical poor (up to 40% strength, easy to secondary injury).Therefore, it is of great clinical significance to find a new method of tendon regeneration and repair.In recent years, the development of stem cells and tissue engineering technology has brought a new opportunity to improve the quality of soft tissue repair, such as tendons. People began to try to use tendon tissue engineering technology to treat and repair tendon defects.Seed cells are one of the key elements in tissue engineering.Currently, seed cells in tendon tissue engineering include embryonic stem cells ESCs, mesenchymal stem cells (MSCs) and tendon stem cells (TSPCs).However, it has been found that the tendon repaired with stem cells as seed cells is still different from the normal tendon in terms of mechanical properties, and the microstructure of the tendon is characterized by the formation of a large number of small diameter collagen fibers.These small diameter collagen fibers are the direct factors leading to the lower mechanical properties of the tendon.These results suggest that the current tissue engineering methods can only partially improve the quality of tendon repair and lack of effective means to make stem cells fully differentiate into functional tendon cells to achieve complete tendon regeneration.This paper is based on the previous research in our laboratory and found that embryonic stem cells can be used as seed cells of tendon.After directional differentiation of embryonic stem cells into MSCs, the study of tendon tissue engineering and the search for important regulatory factors for early development of tendon were carried out to promote tendon differentiation and repair, with the ultimate aim of regulating tendon differentiation of embryonic stem cells.To construct tissue engineered tendon to promote tendon repair and regeneration.The main contents of this thesis are as follows: the first part is about the construction of tissue engineered tendon by embryonic stem cells (ESC) for tendon repair.The mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) and reticular-silk collagen composite scaffolds were used to construct tissue engineered tendons for tendon repair.The second part is about the selection of important genes related to tendon differentiation.Through the research of developmental biology, we divide tendon development and maturation into different stages for the first time, evaluate the changes of tissue morphology and intrinsic molecular signal during normal development of tendon, and screen them with biochip data.It was found that fos gene played an important role in the process of tendon differentiation, and was further verified by gene overexpression and gene silencing.The third part is the research of fos gene used to differentiate embryonic stem cells into early tendon.Fos gene was overexpressed in mesenchymal stem cells derived from embryonic stem cells to promote the differentiation of cells into early tendon.The results and findings of this study provide a new experimental basis and knowledge of differentiation for the repair of regenerated tendons using embryonic stem cells. According to tendon development, the periodic differentiation of tendons is proposed as a means of inducing tendon tissue engineering.To bring new seed cells and techniques for the treatment of tendon injury in the future.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R686

【共引文獻(xiàn)】

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