酶诱导分子自组装的水凝胶应用于间充质干细胞促血管新生的研究

Stem cell treatment for a hind limb ischemia yields a limited therapeutic effect due to cell loss and apoptosis caused by local ischemic microenvironment. Hydrogel formed by self-assembly of small molecular peptides hold great promise for cell biomimetic scaffold and delivery vehicles due to their advantages over traditional biomaterials including good biocompatibility and degradation. In this proposal, we plan to synthesize a hydrogels formed by the enzyme- induced self-assembly of small molecule may enhance neovascularization via mimicking the components of stem cell niche, which will be followed by preparation of the materials in the aqueous solubility as the encapsulation matrix. Furthermore, mesenchymal stem cells （MSCs） were labelled with the double fusion reporter gene that consists of firefly luciferase and green fluorescence protein, which be used as noninvasive molecular imaging to real-time monitor and trace the behavior and long-term engraftment of administrated stem cells. Moreover, we assessed the proangiogenic potential of mesenchymal stem cells, anti-apoptotic and recovery limb function, which co-transplantation of hydrogels and MSCs into a murine model of hind limb ischemia. This study will open up new opportunities for the development of promising cell delivery for the clinical translation of MSCs-based therapeutics.

局部缺血微环境中移植干细胞易于流失和凋亡的问题,导致干细胞治疗下肢缺血的疗效有限。相比于传统的生物材料,小分子多肽自组装形成的水凝胶具有良好的生物相容性和可降解等优点,在干细胞培养支架和载体等应用中拥有巨大的潜力。本项目拟合成一种酶催化诱导和多肽自组装形成的水凝胶，并采用水溶性好的材料作为封端基质，用于模拟干细胞生长的微环境而促进血管新生。在此基础上，拟通过双融合报告基因标记间充质干细胞，结合非侵入的分子影像手段长时间动态的观察间充质干细胞在移植后的行为和生物学特性；同时，研究移植的水凝胶与间充质干细胞在小鼠下肢缺血模型移植后促血管新生、抗凋亡和修复损伤组织的机理，为开发性质更加优良的干细胞载体向临床转化打下基础。

局部缺血微环境中移植干细胞易于流失和凋亡的问题,导致干细胞治疗下肢缺血的疗效有限。本项目应用酶催化诱导多肽自组装形成的水凝胶，采用水溶性好的材料作为封端基质作为干细胞移植载体，结合双融合报告基因标记移植的间充质干细胞系，利用分子影像学方法监测干细胞在体内的存活、增殖、迁移、分化及功能改变，探讨在小鼠下肢缺血疾病模型中干细胞的作用机理，根据不同的细胞移植方法对疾病模型指标的检测，显示出良好的促血管新生能力，对干细胞载体在再生医学中应用潜能提供了客观的认识。发表了SCI收录论文1篇，其中1篇Mol Med Rep，获得宁夏医院管理协会第四届优秀论文二等奖。培养研究生2名。通过本项目的实施培养干细胞和分子影像的科研队伍。