小分子水凝胶承载双基因修饰的MMSCs移植治疗心肌梗塞及其机制探讨

干细胞治疗心肌梗死存在移植后细胞滞留率、存活率和分化率低的问题是目前制约其发展的瓶颈。水凝胶可模拟心肌内环境作为干细胞三维载体支架，经移植治疗心梗可明显提高细胞的滞留、存活和分化并改善心功能。我们前期研究制备了一系列小分子水凝胶，发现其在细胞三维培养、干细胞分化基因调控、创伤修复、肝组织修复及药物控释等领域显现了良好的应用前景，然而，小分子水凝胶在心脏修复中的应用尚未广泛开展；我们同时发现经BCL2和VEGF165双基因修饰的骨髓间充质干细胞（MMSCs）可提高细胞的存活并促进血管新生。为了进一步明确小分子水凝胶在心脏修复中的作用以期获得更好的疗效，本研究拟采用活性小分子水凝胶承载BCL2和VEGF165双基因修饰的MMSCs移植治疗心肌梗死，通过观察其对MMSCs粘附、增殖、分化的影响，评价其移植后的疗效，阐明其促进心肌修复的机制，为可注射性心肌组织工程治疗心梗奠定材料学基础。

The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, low rate of cells retention, survival and differentiation after transplantation are the major challenges for its development. Numbers of studies have found that hydrogels can mimic cardiac microenvironment and be used as a carrier of stem cells in three-dimensional environment. Moreover, transplantation of stem cells and hydrogels complex in the treatment of MI can significantly improve stem cells retention, survival and differentiation in the infarcted zone and thereby ameliorate cardiac function. We have synthesize series of small molecular hydrogels, which have shown a great prospect in three-dimensional cell culture, gene regulation of stem cells differentiation, liver tissue repair, wound healing as well as drug controlled delivery, however, its potential utility and mechanism in cardiac regeneration have yet to be tested. Besides, our previous works found that BCL2 and VEGF165 double gene-modified bone marrow mesenchymal stem cells(MMSCs) can dramatically promote the expression of cell survival and angiogenesis factors..In order to explore the roles of small molecular hydrogels in the treatment of MI, we will used electroactive small molecular hydrogels as three-dimensional cell culture scaffolds. In vitro, the adhesion, proliferation, differentiation of MMSCs cultured in this scaffolds will be characterized. Then, the small molecular hydrogels and/or BCL2 and VEGF165 double gene-modified MMSCs will be injected in the animal infarcted sites to explore its cardiac tissue repair potential. Our aims is to investigate the roles of small molecular hydrogels in preserving cardiac function,and clarify its underlying mechanism of cardiac tissue repair. This study, focused on the injectable cardiac tissue engineering strategy in the treatment of MI, is promising to lay a firm foundation for the biomaterials science.