间充质干细胞
旁分泌信号
外体
心肌梗塞
干细胞
再生(生物学)
医学
细胞
心功能曲线
心包腔
细胞疗法
微泡
生物医学工程
细胞生物学
心脏病学
化学
病理
心力衰竭
内科学
心包
生物
小RNA
生物化学
受体
基因
作者
Junlang Li,Yongbo Lv,Dashuai Zhu,Xuan Mei,Ke Huang,Xianyun Wang,Zhenhua Li,Sichen Zhang,Shiqi Hu,Kristen D. Popowski,Ke Cheng,Juan Wang
标识
DOI:10.1016/j.cej.2021.131581
摘要
Although cell therapy has shown potential efficacy in the treatment of heart diseases, one challenge is low cellular retention rate and poor engraftment. We sought to perform a head-to-head comparison on cell retention and therapeutic benefits of intramyocardial (IM) injection and intrapericardial cavity (IPC) injection of adult stem cells in hydrogel. Mouse green fluorescent protein (GFP)-labeled mesenchymal stem cells (MSCs) were combined in extracellular matrix (ECM) hydrogel and injected into the pericardial cavity or the myocardium of the heart of C57BL/6 mice that had been subjected to a myocardial infarction. The IPC injection, as an alternative cell delivery route, led to better cardiac function in our mouse model with myocardial infarction, which was showed by echocardiographies in the short term (2 weeks) and the long term (6 weeks). This result was attributed to 10-fold higher engraftment of MSCs injected via IPC route (42.5 ± 7.4%) than that of MSCs injected intramyocardially (4.4 ± 1.3%). Immunohistochemistry data revealed better cellular proliferation, less apoptosis, and better vascular regeneration in the myocardium after IPC delivery of MSCs. CD63-RFP exosome labeling system showed that heart cells including cardiomyocytes absorbed MSC-exosomes at higher rates when MSCs were injected via IPC route, compared to the results from IM injections, indicating more extensive paracrine activity of MSCs after IPC injections. What is more, the feasibility and safety of IPC injection were demonstrated in a porcine model with minimally invasive procedure. Intrapericardial cavity injection gave a promising solution for the low retention issue of MSCs in the infarcted heart.
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