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注射用包封脐带间充质干细胞的甲基丙烯酸明胶/氧化葡聚糖导电水凝胶用于心肌梗死治疗

Injectable conductive gelatin methacrylate / oxidized dextran hydrogel encapsulating umbilical cord mesenchymal stem cells for myocardial infarction treatment.

作者信息

Zhu Shuoji, Yu Changjiang, Liu Nanbo, Zhao Mingyi, Chen Zerui, Liu Jian, Li Ge, Huang Huanlei, Guo Huiming, Sun Tucheng, Chen Jimei, Zhuang Jian, Zhu Ping

机构信息

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510100, China.

出版信息

Bioact Mater. 2021 Nov 17;13:119-134. doi: 10.1016/j.bioactmat.2021.11.011. eCollection 2022 Jul.

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 S/cm) was similar to that of natural heart tissue. 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 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)移植已被提出作为治疗心肌梗死(MI)的一种有前景的治疗方式,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修复梗死心肌和恢复心脏功能的细胞递送载体是非常理想的。在这项工作中,我们开发了一种基于甲基丙烯酸明胶(GelMA)和氧化葡聚糖(ODEX)的水凝胶系统作为MI的细胞递送载体。多巴胺可作为氧化石墨烯(GO)的还原剂形成还原型GO(rGO)。通过调整rGO的量,rGO浓度为0.5mg/mL的水凝胶的电导率(≈10S/cm)与天然心脏组织相似。细胞实验表明,所制备的水凝胶具有优异的生物相容性和UCMSCs的细胞递送能力。更重要的是,GelMA-O5/rGO水凝胶可以促进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。进一步的实验表明,与PBS组相比,GelMA-O5/rGO/UCMSCs水凝胶可以显著提高大鼠的射血分数(EF),显著减少心肌梗死面积,促进UCMSCs的存活,增强cTnI和Cx43的表达水平,并降低caspase-3的表达水平。本研究结果表明,包裹UCMSCs的可注射导电GelMA-O5/rGO水凝胶可以改善受损心肌组织并重建心肌功能,这将是一种有前景的心脏修复治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ebe/8844712/7a5ccd2fabc7/ga1.jpg

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