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In situ activated mesenchymal stem cells (MSCs) by bioactive hydrogels for myocardial infarction treatment.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-07-14 , DOI: 10.1039/d0tb01320j
Long Gao 1 , Min Yi , Min Xing , Hekai Li , Yanling Zhou , Qing Xu , Zhaowenbin Zhang , Zhanpeng Wen , Jiang Chang
Affiliation  

Stem-cell therapy has been proved as a promising strategy for myocardial infarction (MI) treatment. However, the therapeutic efficacy is mainly limited by the cellular activity of transplanted mesenchymal stem cells (MSCs). In this study, a novel bioglass (BG)/γ-polyglutamic acid (γ-PGA)/chitosan (CS) hydrogel was obtained by in situ adding BG to stimulate the imine bond formation. And the effect of the composite hydrogel on MI therapeutic efficacy was evaluated in a rat acute myocardial infarction (AMI) model in vivo and the possible mechanism of the BG/γ-PGA/CS hydrogel for the stimulation of the intercellular interaction between MSCs and cardiomyocytes (CMs) was explored by a MSC and CM co-culture experiment in vitro. The implantation of the MSC loaded BG/γ-PGA/CS composite hydrogel in the mice AMI model showed a significant improvement in the therapeutic efficacy with improved cardiac function, attenuation of heart remodeling, reduced cardiomyocyte apoptosis and accelerated vascularization. The in vitro cell experiments demonstrated that the BG/γ-PGA/CS hydrogel activated the intercellular interaction between MSCs and CMs, which resulted in reduced cell apoptosis and enhanced angiogenesis. Silicate based bioactive hydrogels activated MSCs and cell–cell interactions in cardiac tissue after AMI and significantly enhanced the efficacy, which suggests that this bioactive hydrogel based approach is an effective way to enhance stem-cell therapy.

中文翻译:

通过生物活性水凝胶原位激活的间充质干细胞(MSC)用于心肌梗死的治疗。

干细胞疗法已被证明是心肌梗塞(MI)治疗的一种有前途的策略。但是,治疗功效主要受到移植的间充质干细胞(MSCs)的细胞活性的限制。在这项研究中,通过原位添加BG刺激亚胺键的形成,获得了一种新型的生物玻璃(BG)/γ-聚谷氨酸(γ-PGA)/壳聚糖(CS)水凝胶。并在大鼠急性心肌梗死(AMI)模型评估了复合水凝胶对MI治疗功效的影响以及BG /γ-PGA/ CS水凝胶刺激MSC与心肌细胞间相互作用的可能机制(CMs)通过MSC和CM共培养实验进行了体外探索。在小鼠AMI模型中植入MSC加载的BG /γ-PGA/ CS复合水凝胶显示出显着的治疗效果,改善了心脏功能,减轻了心脏重塑,减少了心肌细胞凋亡并加速了血管形成。在体外细胞实验表明,BG /γ-PGA / CS凝胶活化MSC和CM之间的间相互作用,这导致减少的细胞凋亡和增强的血管生成。基于硅酸盐的生物活性水凝胶可激活AMI后心脏组织中的MSC和细胞间相互作用,并显着增强疗效,这表明这种基于生物活性水凝胶的方法是增强干细胞治疗的有效途径。
更新日期:2020-09-02
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