Yuan Zihui, Tan Juan, Wang Jian
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Int J Stem Cells. 2024 Feb 28;17(1):70-79. doi: 10.15283/ijsc22209. Epub 2023 Oct 19.
The efficacy of adipose-derived stem cells (ASCs) on myocardial infarction is limited due to poor survival and engraftment. Integrin-mediated cell adhesion is a prerequisite for its survival and homing. ASCs expressed insufficient integrin , limiting their homing capacity. This study aims to characterize integrin ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin ASCs subpopulation, which were characterized and transplanted into myocardial infarction model. Positron emission tomography imaging were performed to measure infarction size. Cardiac cine magnetic resonance imaging was used to evaluate heart contractile function. Compared with the unfractionated ASCs, integrin ASCs subpopulation secreted a higher level of angiogenic growth factors, migrated more rapidly, and exhibited a stronger anti-apoptotic capacity. Vascular cell adhesion molecule-1 was obviously up-regulated at 3 days after myocardial infarction, which interacted with integrin receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin ASCs subpopulation into the 3-day infarcted myocardium. Integrin ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin ASCs subpopulation is superior to unfractionated ASCs in ameliorating ischemic myocardial damage in animal model. Mechanistically, their more robust engraftment into the infarct area, higher migratory capacity and their increased release of paracrine factors contribute to enhanced tissue repair.
由于存活率低和归巢能力差，脂肪来源干细胞（ASC）对心肌梗死的疗效有限。整合素介导的细胞黏附是其存活和归巢的前提条件。ASC表达的整合素不足，限制了它们的归巢能力。本研究旨在鉴定整合素阳性ASC亚群，并研究它们在心肌梗死中的治疗效果。我们使用荧光激活细胞分选技术收获整合素阳性ASC亚群，对其进行鉴定并移植到心肌梗死模型中。进行正电子发射断层扫描成像以测量梗死面积。使用心脏电影磁共振成像评估心脏收缩功能。与未分选的ASC相比，整合素阳性ASC亚群分泌更高水平的血管生成生长因子，迁移更快，并表现出更强的抗凋亡能力。心肌梗死后3天血管细胞黏附分子-1明显上调，它与ASC表面的整合素受体相互作用以增强存活和黏附。因此，我们将未分选的ASC或整合素阳性ASC亚群植入梗死3天的心肌中。整合素阳性ASC亚群在梗死心肌中的植入更稳固。与未分选的ASC相比，整合素阳性ASC亚群更有效地减小梗死面积并加强心脏功能恢复。在改善动物模型中的缺血性心肌损伤方面，整合素阳性ASC亚群优于未分选的ASC。从机制上讲，它们在梗死区域更稳固的植入、更高的迁移能力以及旁分泌因子释放的增加有助于增强组织修复。
