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 α₄, limiting their homing capacity. This study aims to characterize integrin α₄^＋ ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin α₄^＋ ASCs subpopulation, which were characterized in vitro 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 α₄^＋ 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 α₄ receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin α₄^＋ ASCs subpopulation into the 3-day infarcted myocardium. Integrin α₄^＋ ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin α₄^＋ ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin α₄^＋ 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.

中文翻译：

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脂肪干细胞中的整合素 α4 阳性亚群通过增强心肌梗塞的植入，有效减少梗塞面积。

由于存活率和植入能力较差，脂肪干细胞（ASC）对心肌梗死的疗效有限。整合素介导的细胞粘附是其生存和归巢的先决条件。ASC 表达不足的整合素 α ₄，限制了它们的归巢能力。本研究旨在表征整合素α ₄ ^＋ ASC 亚群并探讨其对心肌梗死的治疗效果。我们采用荧光激活细胞分选法收集整合素α ₄ ^＋ ASCs 亚群，对其进行体外表征并移植到心肌梗死模型中。进行正电子发射断层扫描成像来测量梗塞面积。心脏电影磁共振成像用于评估心脏收缩功能。与普通ASCs相比，整合素α ₄ ^＋ ASCs亚群分泌的血管生长因子水平更高，迁移更快，抗凋亡能力更强。心肌梗死后3天血管细胞粘附分子1明显上调，与ASC表面整合素α4受体相互作用，增强其存活和粘附_。因此，我们将未分割的ASCs或整合素α ₄ ^＋ ASCs亚群植入到梗死3天的心肌中。整合素α ₄ ^＋ ASCs 亚群在梗塞心肌中表现出更强的植入能力。整合素α ₄ ^＋ ASCs 亚群比未分割的ASCs 更能有效地减少梗塞面积并增强心功能恢复。整合素α ₄ ^＋ ASCs亚群在改善动物模型缺血性心肌损伤方面优于普通ASCs。从机制上讲，它们更牢固地植入梗塞区域、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。