PDF(Pubmed)
Abstract：
Umbilical cord mesenchymal stem cells (UCMSCs) transplantation has been proposed as a promising treatment modality for myocardial infarction (MI), but the low retention rate remains a considerable challenge. Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function. In this work, we developed a hydrogel system based on gelatin methacrylate (GelMA) and oxidized dextran (ODEX) as cell delivery vehicles for MI. And dopamine could be used as a reductant of graphene oxide (GO) to form reductive GO (rGO). By adjusting the amount of rGO, the conductivity of hydrogels with 0.5 mg/mL rGO concentration (≈10-4 S/cm) was similar to that of natural heart tissue. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs. More importantly, GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation, improve the myocardial differentiation ability of UCMSCs, and up-regulate the expression of cTnI and Cx43. Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction (EF) of rats and significantly reduce myocardial infarct area compared to PBS group, promote the survival of UCMSCs, enhance the expression level of cTnI and Cx43, and decrease the expression level of caspase-3. The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function, which will be a promising therapeutic strategy for cardiac repair.
摘要：
脐带间充质干细胞（UCMSCs）移植已被认为是心肌梗死（MI）的一种有希望的治疗方式。但低保留率仍然是一个相当大的挑战。具有导电能力的可注射天然聚合物水凝胶作为细胞递送载体以修复梗塞心肌并恢复心脏功能是非常理想的。在这项工作中,我们开发了基于明胶甲基丙烯酸酯(GelMA)和氧化葡聚糖(ODEX)的水凝胶系统作为MI的细胞递送载体。多巴胺可以作为氧化石墨烯(GO)的还原剂形成还原性GO(rGO)。通过调整rGO的数量，rGO浓度为0.5mg/mL（≈10-4S/cm）的水凝胶的电导率与天然心脏组织相似。体外细胞实验表明,所制备的水凝胶对UCMSCs具有良好的生物相容性和细胞递送能力。更重要的是,GelMA-O5/rGO水凝胶可促进UCMSCs的生长和增殖,提高UCMSCs的心肌分化能力,并上调cTnI和Cx43的表达。进一步的体内实验表明，与PBS组相比，GelMA-O5/rGO/UCMSCs水凝胶能显著改善大鼠射血分数(EF)，显著减少心肌梗死面积。促进UCMSCs的存活，提高cTnI和Cx43的表达水平,降低caspase-3的表达水平。这项研究的结果表明，可注射的导电GelMA-O5/rGO水凝胶包裹UCMSCs可以改善受损的心肌组织和重建心肌功能，这将是一个有前途的心脏修复治疗策略。
