Injectable biodegradable hydrogels for embryonic stem cell transplantation: improved cardiac remodelling and function of myocardial infarction.

Injectable biodegradable hydrogels for embryonic stem cell transplantation: improved cardiac remodelling and function of myocardial infarction.
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用于胚胎干细胞移植的可注射生物降解水凝胶:改善心脏重塑和心肌梗塞功能。

DOI:
10.1111/j.1582-4934.2011.01409.x
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发表时间:
2012-06
影响因子:
5.3
通讯作者:
Wang C
Wang C
中科院分区:
医学2区
文献类型:
--
作者:
Wang H;Liu Z;Li D;Guo X;Kasper FK;Duan C;Zhou J;Mikos AG;Wang C

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在这项研究中,研究了一种可注射的、可生物降解的低聚富马酸乙二醇水凝胶复合物(OPF)作为小鼠胚胎干细胞(mESCs)的载体,用于治疗心肌梗死(MI)。使用OPF水凝胶包封mESCs。免疫组化检测体外培养14 d后细胞分化情况。然后,将包裹在OPF水凝胶中的mESCs注射到大鼠心肌梗死模型左室壁上。采用详细的组织学分析和超声心动图来确定移植4周后的结构和功能后果。在抗坏血酸诱导下,在OPF水凝胶中,mESCs可以分化为心肌细胞和其他三种细胞类型。移植后,OPF + ESC组24小时细胞保留率和4周移植物大小均显著高于PBS + ESC组(P < 0.01)。移植后4周,单独使用OPF水凝胶可显著减少梗死面积和胶原沉积,改善心功能。与PBS + ESC、OPF和PBS组比较,OPF + ESC组心功能和血运重建明显改善,梗死面积和纤维化面积明显缩小(P < 0.01)。与PBS对照组相比,所有处理均显著降低了MMP2和MMP9蛋白水平,Western blotting结果显示,OPF + ESC组的MMP2和MMP9蛋白水平下降最多。移植的mESCs表达心血管标志物。这项研究表明,利用OPF水凝胶进行干细胞包封和移植的心脏再生方法具有潜力。
In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation.
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