Heart Repair Using Nanogel-Encapsulated Human Cardiac Stem Cells in Mice and Pigs with Myocardial Infarction.

Heart Repair Using Nanogel-Encapsulated Human Cardiac Stem Cells in Mice and Pigs with Myocardial Infarction.
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使用纳米凝胶封装的人类心脏干细胞修复患有心肌梗塞的小鼠和猪的心脏

DOI:
10.1021/acsnano.7b01008
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发表时间:
2017-10-24
期刊:
影响因子:
17.1
通讯作者:
Cheng K
Cheng K
中科院分区:
材料科学1区
文献类型:
--
作者:
Tang J;Cui X;Caranasos TG;Hensley MT;Vandergriff AC;Hartanto Y;Shen D;Zhang H;Zhang J;Cheng K

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干细胞移植目前已在临床上应用,但受到移植细胞留存和植入率低以及使用同种异体或异种细胞时炎症和免疫反应的不良影响的限制。在此,我们在小鼠和猪的心肌梗死(MI)模型中证明了将人心脏干细胞(hCSCs)包裹在热敏性聚(N - 异丙基丙烯酰胺 - 共 - 丙烯酸)或P(NIPAM - AA)纳米凝胶中的安全性和有效性。与在生理盐水中注射异种hCSCs不同,在免疫功能正常的小鼠中注射纳米凝胶包裹的hCSCs不会引发全身炎症或局部T细胞浸润。在患有急性心肌梗死的小鼠和猪中,注射包裹的hCSCs可保护心脏功能并减小疤痕面积,而在生理盐水中注射hCSCs则对心脏愈合有不良影响。总之,热敏性纳米凝胶可用作干细胞载体:其多孔且复杂的内部结构允许营养物质、氧气和分泌物扩散,但可防止干细胞受到免疫细胞的攻击。
Stem cell transplantation is currently implemented clinically but is limited by low retention and engraftment of transplanted cells and the adverse effects of inflammation and immunoreaction when allogeneic or xenogeneic cells are used. Here, we demonstrate the safety and efficacy of encapsulating human cardiac stem cells (hCSCs) in thermosensitive poly(N-isopropylacrylamine-co-acrylic acid) or P(NIPAM-AA) nanogel in mouse and pig models of myocardial infarction (MI). Unlike xenogeneic hCSCs injected in saline, injection of nanogel-encapsulated hCSCs does not elicit systemic inflammation or local T cell infiltrations in immunocompetent mice. In mice and pigs with acute MI, injection of encapsulated hCSCs preserves cardiac function and reduces scar sizes, whereas injection of hCSCs in saline has an adverse effect on heart healing. In conclusion, thermosensitive nanogels can be used as a stem cell carrier: the porous and convoluted inner structure allows nutrient, oxygen, and secretion diffusion but can prevent the stem cells from being attacked by immune cells.
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