Department of Cardiology, the Ninth Hospital Affiliated to Medical College, Shanghai Jiaotong University, ShangHai, China.
Int J Cardiol. 2012 Jan 12;154(1):2-8. doi: 10.1016/j.ijcard.2011.05.078.
This study assessed the potential therapeutic efficacy of endothelial NO syntheses (eNOS)-expressing adipose tissue-derived stem cells (ADSCs) on infarcted hearts. We isolated CD29+, CD44+, CD45- cells from adipose tissue. Multipotent property of ADSCs was characterized by induction to differentiate into myogenic, neurogenic, and endothelic lineages. We hypothesized that combination of eNOS over-expression and transplantation of ADSCs could restore NO bioavailability and improve cardiac function in infarcted hearts. Here with several lines of experimental evidences, we demonstrated that ADSCs with eNOS overexpression induced eNOS expression in host endothelial cells and vascular smooth muscle cells, both in vitro and in vivo. This effect was possibly mediated by calcium signal. Transplantation of ADSCs with eNOS embedded showed great therapeutic efficacy in reduction of infarcted size, compared with normal ADSC. Results of this study suggest that ADSCs could be an attractive vehicle for the exogenous eNOS expression into heart after infarction, which is beneficial to restoration of cardiac function. Paracrine effect by mobilizing the host endothelial cells and smooth muscle cells may be the mechanism underlying the therapeutic effect.
本研究评估了内皮型一氧化氮合酶（eNOS）表达的脂肪组织来源干细胞（ADSCs）在梗死心脏中的潜在治疗功效。我们从脂肪组织中分离出 CD29+、CD44+、CD45-细胞。ADSCs 的多能性通过诱导分化为肌源性、神经源性和内皮谱系来表征。我们假设 eNOS 过表达与 ADSC 移植的结合可以恢复梗死心脏中的 NO 生物利用度并改善心功能。通过一系列实验证据，我们证明了 eNOS 过表达的 ADSC 可以在体外和体内诱导宿主内皮细胞和血管平滑肌细胞中 eNOS 的表达。这种效应可能是通过钙信号介导的。与正常 ADSC 相比，嵌入 eNOS 的 ADSC 移植在减少梗死面积方面显示出了很好的治疗效果。这项研究的结果表明，ADSCs 可能是一种有吸引力的载体，可以在梗死后将外源性 eNOS 表达到心脏中，这有利于恢复心功能。通过动员宿主内皮细胞和平滑肌细胞的旁分泌作用可能是其治疗效果的机制。
