Tailorable Hydrogel Improves Retention and Cardioprotection of Intramyocardial Transplanted Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice
Tailorable Hydrogel Improves Retention and Cardioprotection of Intramyocardial Transplanted Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice
复制标题
可定制水凝胶可改善心肌内移植间充质干细胞的保留和心脏保护作用，用于治疗小鼠急性心肌梗塞
DOI：
10.1161/jaha.119.013784
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发表时间：
2020-01-21
影响因子：
5.4
通讯作者：
Tao, Ling
中科院分区：
文献类型：
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作者：
Chen, Youhu;Li, Congye;Tao, Ling
背景心肌内干细胞的植入不良限制了其对心肌梗死（MI）引起的心脏损伤的治疗效率。转谷氨酰胺酶交联明胶 (Col-Tgel) 是一种可定制的胶原蛋白水凝胶，正在成为体内细胞递送的优异生物材料支架。在这里，我们测试了 Col-Tgel 增加心肌内注射干细胞的保留，从而减少 MI 后心脏损伤的假设。 方法和结果将脂肪源性间充质干细胞 (ADSC) 与 Col-Tgel 在体外 3 维系统中共培养，并使用扫描电子显微镜和共聚焦观察 Col-Tgel 封装的 ADSC 显微镜。评估了共培养的 ADSC 的活力、增殖和迁移。此外，对小鼠进行MI并心肌内注射ADSC、Col-Tgel或其组合。评估了 ADSC 的植入、存活、心脏功能和纤维化。体外 MTT 和 Cell Counting Kit-8 测定表明 ADSC 在 Col-Tgel 中存活并增殖长达 4 周。此外，MTT 和 Transwell 检测显示 ADSC 迁移到 Col-Tgel 球体边缘之外。此外，与单独的ADSCs相比，Col-Tgel封装的ADSCs显着增强了ADSCs对心肌梗死引起的心脏损伤的长期保留和心脏保护作用。结论在本研究中，我们成功建立了ADSCs和Col-Tgel的3维共培养系统。 Col-Tgel 为 ADSC 长期保留在缺血区域创造了合适的微环境，从而增强了其心脏保护作用。总而言之，这项研究可能为基于干细胞的治疗缺血性心脏病的疗法提供替代生物材料。
BackgroundPoor engraftment of intramyocardial stem cells limits their therapeutic efficiency against myocardial infarction (MI)-induced cardiac injury. Transglutaminase cross-linked Gelatin (Col-Tgel) is a tailorable collagen-based hydrogel that is becoming an excellent biomaterial scaffold for cellular delivery in vivo. Here, we tested the hypothesis that Col-Tgel increases retention of intramyocardially-injected stem cells, and thereby reduces post-MI cardiac injury.Methods and ResultsAdipose-derived mesenchymal stem cells (ADSCs) were co-cultured with Col-Tgel in a 3-dimensional system in vitro, and Col-Tgel encapsulated ADSCs were observed using scanning electron microscopy and confocal microscopy. Vitality, proliferation, and migration of co-cultured ADSCs were evaluated. In addition, mice were subjected to MI and were intramyocardially injected with ADSCs, Col-Tgel, or a combination thereof. ADSCs engraftment, survival, cardiac function, and fibrosis were assessed. In vitro MTT and Cell Counting Kit-8 assays demonstrated that ADSCs survive and proliferate up to 4 weeks in the Col-Tgel. In addition, MTT and transwell assays showed that ADSCs migrate outside the edge of the Col-Tgel sphere. Furthermore, when compared with ADSCs alone, Col-Tgel-encapsulated ADSCs significantly enhanced the long-term retention and cardioprotective effect of ADSCs against MI-induced cardiac injury.ConclusionsIn the current study, we successfully established a 3-dimensional co-culture system using ADSCs and Col-Tgel. The Col-Tgel creates a suitable microenvironment for long-term retention of ADSCs in an ischemic area, and thereby enhances their cardioprotective effects. Taken together, this study may provide an alternative biomaterial for stem cell-based therapy to treat ischemic heart diseases.