The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment
The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment
复制标题
壳聚糖水凝胶对缺血心肌微环境中干细胞植入、存活和归巢的影响
DOI：
10.1016/j.biomaterials.2011.12.044
复制
发表时间：
2012-04-01
期刊：
影响因子：
14
通讯作者：
Wang, Changyong
中科院分区：
文献类型：
--
作者：
Liu, Zhiqiang;Wang, Haibin;Wang, Changyong
细胞心肌成形术治疗心肌梗死(MI)的一个挑战是如何改善MI的微环境以促进干细胞的植入、存活和归巢以促进心肌修复。可注射水凝胶的应用是一种有效的策略。然而，可注射支架在改善心肌梗死微环境、为细胞存活、植入和归巢提供空间和指导方面的作用尚未得到深入研究。我们探索了一种可注射的壳聚糖水凝胶，用于干细胞进入缺血心脏，并研究了该水凝胶的有益作用和机制。在体外，用过氧化氢处理来模拟活性氧(ROS)的微环境。分析ROS和壳聚糖组分对脂肪间充质干细胞(ADSCs)的保护作用。在体内，结扎SD大鼠左前降支造成心肌梗死。将PBS、壳聚糖水凝胶、ADSC/PBS和ADSC/壳聚糖水凝胶分别注入心肌梗死边缘。采用多种技术评价壳聚糖水凝胶在移植后的益处。我们观察到，缺血产生的ROS会损害ADSC的黏附分子，包括整合素相关的黏附分子整合素αV和β1，局灶性黏附相关分子p-FAK和p-Src，以及宿主心肌ICAM 1和VCAM1的相应配体。壳聚糖水凝胶可以通过清除ROS来挽救这些分子，并募集干细胞归巢的关键趋化因子，如SDF-1。提示壳聚糖水凝胶可通过清除ROS和趋化因子募集，改善心肌梗死微环境，促进干细胞在缺血心脏的植入、存活和归巢，促进心肌修复。(C)2011爱思唯尔有限公司。保留所有权利。
One challenge of cellular cardiomyoplasty for myocardial infarction (MI) is how to improve MI microenvironment to facilitate stem cell engraftment, survival and homing for myocardial repair. The application of injectable hydrogels is an effective strategy. However, it has not been thoroughly investigated on the role of the injectable scaffolds, in improving MI microenvironment, providing space and guidance for cell survival, engraftment and homing. We explored an injectable chitosan hydrogel for stem cell delivery into ischemic heart and investigated the beneficial effects and mechanisms of the hydrogel. In vitro, H2O2-treatment was used to mimic reactive oxygen species (ROS) microenvironment. The influence of ROS and protection of chitosan components on adipose-derived mesenchymal stem cells (ADSCs) was analyzed too. In vivo, MI was induced by the left anterior descending artery ligation in SD rats. PBS, chitosan hydrogel, ADSC/PBS and ADSC/chitosan hydrogel were injected into the border of infracted hearts respectively. Multi-techniques were used to assess the beneficial effects of chitosan hydrogel after transplantation. We observed that ROS generated by ischemia would impair ADSC adhesion molecules, including integrin-related adhesion molecules integrin alpha V and beta 1, focal adhesion-related molecules p-FAK and p-Src, and corresponding ligands of host myocardium ICAM1 and VCAM1. Chitosan hydrogel could rescue these molecules through ROS scavenging and recruit key chemokine for stem cell homing, such as SDF-1. The results suggest that chitosan hydrogel could improve MI microenvironment, enhance stem cell engraftment, survival and homing in ischemic heart through ROS scavenging and chemokine recruitment, contributing to myocardial repair. (c) 2011 Elsevier Ltd. All rights reserved.