ABSTRACT

Adipose-derived stem cell (AdSC) has been attracting attention as a convenient stem cell source. Not only AdSC can differentiate into various tissue cells, but it can also accelerate cell proliferation, anti-inflammation, and angiogenesis by secreting paracrine factors. Studies have demonstrated AdSC treatment of ischemic heart. However, an improvement in the remaining live AdSCs administered at the injected site while maintaining paracrine factor secretion is desired to achieve effective regenerative medicine. We previously reported the ABA-type tri-block copolymer of poly(ɛ-caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG), exhibiting temperature-responsive sol-to-gel transition as biodegradable injectable polymer (IP) systems. Moreover, we recently reported that the biodegradable temperature-triggered chemically cross-linked gelation systems exhibited longer gel state durations using tri-PCG attaching acryloyl groups and a polythiol derivative. In this study, we explored this IP-mediated AdSC delivery system. We investigated the cell viability, mRNA expression, and cytokine secretion of AdSCs cultured in the physical or chemical IP hydrogels. Both of these IP hydrogels retained a certain number of viable cells, and RT-PCR and ELISA analyses revealed that mRNA expression and secretion of vascular endothelial growth factor of the AdSCs cultured in the chemical hydrogel were higher than the physical hydrogel. Moreover, AdSCs injected with the chemical hydrogel into ischemic heart model mice showed longer retention of the cells at the injected site and recovery from the ischemic condition. The results mean that the IP system is a promising candidate for a stem cell delivery system that exhibits the recovery of cardiac function for myocardial infarction treatment.

摘要

脂肪干细胞（AdSC）作为一种方便的干细胞来源而备受关注。AdSC不仅可以分化成各种组织细胞，还可以通过分泌旁分泌因子来加速细胞增殖、抗炎和血管生成。研究表明 AdSC 治疗缺血性心脏。然而，需要改善在注射部位施用的剩余活 AdSC，同时保持旁分泌因子分泌，以实现有效的再生医学。我们之前报道了聚（ε-己内酯-co）的 ABA 型三嵌段共聚物。-乙醇酸）和聚（乙二醇）（tri-PCG），作为可生物降解的可注射聚合物（IP）系统表现出温度响应性溶胶到凝胶的转变。此外，我们最近报道了可生物降解的温度触发的化学交联凝胶系统在使用三-PCG 连接丙烯酰基和多硫醇衍生物时表现出更长的凝胶状态持续时间。在这项研究中，我们探索了这种 IP 介导的 AdSC 传递系统。我们研究了在物理或化学 IP 水凝胶中培养的 AdSC 的细胞活力、mRNA 表达和细胞因子分泌。这两种IP水凝胶都保留了一定数量的活细胞，RT-PCR和ELISA分析显示，化学水凝胶中培养的AdSCs的mRNA表达和血管内皮生长因子的分泌高于物理水凝胶。此外，将化学水凝胶注射到缺血性心脏模型小鼠中的 AdSC 显示出细胞在注射部位的保留时间更长，并从缺血状态中恢复。结果表明，IP 系统是干细胞递送系统的有希望的候选者，该系统表现出心脏功能的恢复，可用于心肌梗塞的治疗。