NGF nanoparticles enhance the potency of transplanted human umbilical cord mesenchymal stem cells for myocardial repair
NGF nanoparticles enhance the potency of transplanted human umbilical cord mesenchymal stem cells for myocardial repair
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NGF纳米颗粒增强移植人脐带间充质干细胞的心肌修复效力
DOI：
10.1152/ajpheart.00855.2020
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发表时间：
2021
影响因子：
4.8
通讯作者：
Ling Gao
中科院分区：
文献类型：
--
作者：
Wei Luo;Yanshan Gong;Fan Qiu;Yi Yuan;Wenwen Jia;Zhongmin Liu;Ling Gao
在这项研究中，我们调查是否人脐带间充质干细胞（hUCMSC）纤维蛋白贴片加载神经生长因子（NGF）聚（乳酸-羟基乙酸）（PLGA）纳米粒子可以提高hUCMSC心肌梗死（MI）的治疗效力。在体外培养条件下，NGF能显著促进hUCMSCs的增殖，减轻缺氧损伤对细胞的毒性和凋亡。NGF还促进hUCMSCs的旁分泌作用，促进血管生成和心肌细胞保护。hUCMSCs中的酪氨酸激酶A（TrkA）和磷酸肌醇3-激酶（PI 3 K）-丝氨酸/苏氨酸蛋白激酶（Akt）信号通路参与了NGF诱导的保护作用。NGF PLGA纳米粒持续释放NGF至少1个月，并对hUCMSCs产生保护作用，与游离NGF相同。在体内，我们处理了无任何物质（MI组）、含有空白PLGA纳米颗粒的无细胞纤维蛋白贴片（MI + OP组）、含有NGF纳米颗粒的无细胞纤维蛋白贴片（MI + NGF组）以及含有空白PLGA纳米颗粒（MI + MSC组）或NGF PLGA纳米颗粒（MSC + NGF组）的hUCMSC纤维蛋白贴片的MI小鼠。在这些组中，MSC + NGF组表现出最好的心脏收缩功能，最小的梗死面积和最厚的心室壁。NGF PLGA纳米颗粒的应用显著改善了移植的hUCMSCs的保留，并增强了其减少心肌细胞凋亡和促进MI后小鼠心脏血管生成的能力。这些发现表明负载NGF PLGA纳米颗粒的hUCMSC纤维蛋白心脏补片具有良好的治疗潜力。NEW & NOTEWORTHYNGF PLGA纳米颗粒可以对hUCMSC发挥保护作用，并通过TrkA-PI 3 K/Akt信号通路促进hUCMSC的旁分泌作用，促进血管生成和心肌细胞保护，与游离NGF相同。将NGF PLGA纳米粒应用于hUCMSC纤维蛋白心脏补片中，可显著提高移植hUCMSC的滞留能力，增强其减少心肌细胞凋亡和促进心肌梗死后小鼠心脏血管新生的能力。
In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hUCMSCs were involved in the NGF-induced protection. NGF PLGA nanoparticles continued to release NGF for at least 1 mo and also exerted a protective effect on hUCMSCs, the same with free NGF. In vivo, we treated MI mice with nothing (MI group), a cell-free fibrin patch with blank PLGA nanoparticles (MI + OP group), a cell-free fibrin patch with NGF nanoparticles (MI + NGF group), and hUCMSC fibrin patches with blank PLGA nanoparticles (MI + MSC group) or NGF PLGA nanoparticles (MSC + NGF group). Among these groups, the MSC + NGF group exhibited the best cardiac contractile function, the smallest infarct size, and the thickest ventricular wall. The application of NGF PLGA nanoparticles significantly improved the retention of transplanted hUCMSCs and enhanced their ability to reduce myocardial apoptosis and promote angiogenesis in the mouse heart after MI. These findings demonstrate the promising therapeutic potential of hUCMSC fibrin cardiac patches loaded with NGF PLGA nanoparticles.NEW & NOTEWORTHYNGF PLGA nanoparticles can exert a protective effect on hUCMSCs and promote the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection through TrkA-PI3K/Akt signaling pathway, the same with free NGF. The application of NGF PLGA nanoparticles in the hUCMSC fibrin cardiac patches can significantly improve the retention of transplanted hUCMSCs and enhance their ability to reduce myocardial apoptosis and promote angiogenesis in the mouse heart after MI.