Cell and gene therapies for tendon healing: how about their prospects?

doi:10.3969/j.issn.2095-4344.2014.38.019

Abstract

Abstract:

BACKGROUND: Various views and methods for prevention of tendon adhesion have emerged in recent years; however, there is still no method that can effectively prevent tendon adhesion.
OBJECTIVE: To conclude the etiology and pathogenesis of tendon adhesion and to introduce several popular methods for prevention of tendon adhesion by means of reviewing relevant literatures published in recent years.
METHODS: PubMed database and VIP database were searched for articles related to etiology, healing method and prevention of tendon adhesion published from January 1992 to January 2014 using the keywords of “tendon Injuries; tendon adhesion; healing; mechanisms; prevention” in English and Chinese, respectively. Finally, 41 articles were included in result analysis.
RESULTS AND CONCLUSION: Studies have suggested that there is a close correlation between the mechanisms of tendon adhesion and tendon healing. Endogenous healing and exogenous healing are contained in the process of tendon healing. Endogenous healing is that fiber cells on the tendon surface promote tendon healing through their own proliferation. Exogenous healing is to form scar tissues through granulation generated by the surrounding tissues of tendons. Different suture methods can also cause different tendon repair processes. The suture method with strong tensile strength and smooth surface is considered to be an effective mean to reduce tendon adhesion. To inhibit exogenous healing, we can increase or decrease the corresponding macromolecular substances. Polymer compounds cannot only be the barrier but also can promote endogenous healing. By introducing the gene and mesenchymal stem cells into the tendon, we can promote tendon healing, which means the cell therapy and gene transfer have become the new way to promote the healing of tendon.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: endon injuries, tissue adhesions, wound healing

CLC Number:

R318

Jiang Hong-tao, Wang Wei, Na Lei, Gao Jun, Gao Yun-feng, Sun Bo, Yu Chang-yu. Cell and gene therapies for tendon healing: how about their prospects?[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(38): 6179-6183.

Figures/Tables 1

2.1 肌腱愈合方式及粘连原因近年来从分子生物学领域进行了大量针对肌腱粘连机制的相关研究。Jaibaji和Branford等[1-2]研究发现，肌腱愈合方式包括肌腱的内源性愈合和外源性愈合两种。内源性愈合是由肌腱表面及内部的肌腱细胞增生，并迁移至相关位置，肌腱表面的纤维细胞经过自身增殖促进肌腱的愈合。该学说认为粘连不是肌腱愈合所经历的必须途径，甚至可通过内源性愈合而避免粘连的发生。Moores等[3]研究阐明了肌腱外源性愈合导致粘连的主要机制：外源性愈合是由肌腱周围组织通过生成肉芽，并长入肌腱断端完成，形成瘢痕愈合，因而会形成肌腱与周围组织程度较深的粘连，有时粘连紧密，难以分离。Koob等[4]认为在肌腱的愈合过程中，两种愈合方式是同时进行的。 Klein等[5]在研究中发现了转化生长因子β1虽能促进肌腱细胞的胶原合成，但增加了术后粘连组织的形成，因此减少转化生长因子β1在损伤肌腱的表达有助于减轻肌腱的粘连。 Derby等[6]发现了肌腱粘连过程中基因的作用，认为在肌腱伤口愈合处、鞘周瘢痕基质内的炎性细胞渗入处一种特殊基因表达增加，产生的表达产物加剧了肌腱的炎性反应，从而加强了外源性愈合，使之出现粘连程度加强，这种基因后来被命名为反应基因1。加之肌腱表面存在一个由Ⅳ型胶原与层粘连蛋白基底膜覆盖的角化上皮细胞层在肌腱断端被破坏，导致粘连形成。 Loiselle，Katzel等[7-8]通过研究证明了基质金属蛋白酶9来源于骨髓并迁移至损伤处，引起了粘连形成，其具体机制仍不明确，但同时还发现一种名为Smad3的蛋白质，这种蛋白质过度表达可使肌腱的粘连程度加剧，但如果通过抑制该蛋白表达的方法，能使肌腱修复时胶原蛋白表达减少，从而减少肌腱修复时瘢痕形成。当前研究已经在很大程度上向人们揭示了肌腱粘连的基本机制，而且相关研究仍在继续，未来将能够在更为微观的层面上对肌腱粘连的机制进行更为精准、详尽的阐释，更为有效的避免肌腱粘连的方法将有可能被发现。 2.2 肌腱愈合及粘连的客观标准 2.2.1 宏观分级汤锦波[9]教授早在1992年就提出的大体肌腱粘连分度，将肌腱的粘连程度分为了5级。0级：缝合处无粘连；Ⅰ级；少量膜样、束带状粘连，局限于缝合处，肌腱滑动略受限；Ⅱ级；小块状或宽带状粘连，局限于缝合处，肌腱滑动部分受限；Ⅲ级：较大面积紧密粘连，"

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