MiRNA-210在低氧培养脂肪干细胞微泡改善鼠后肢缺血中的作用

The adipose stem cells (ASCs) is attractive vehicle for cell-based therapeutics for patients with cardiovascular diseases because of its ease of acquiring and more proliferative potential. However, the mechanism of the proangiogenic effects of ASCs is still not fully understood. There is a growing recognition that a significant proportion of beneficial effects of ASCs therapy may be due to paracrine mediators rather than trans-differentiation. Although the angiogenic effects of paracrine growth factors are well established, cell-released microvesicles (MVs) have been recently described as a new mechanism of intercellular communication. Emerging evidence indicates MVs are specifically targeted to recipient cells to deliver genetic material, mRNA and miRNA, and play a proangiogenic role in the target cells. Our preliminary studies showed that: 1) The MVs from ASCs cultured in hypoxia might promote angiogenesis, 2) Hypoxia preconditioning promoted the MVs secretion from ASCs and upgraded miR-210 level in MVs. The goal of this application is to unravel the proangiogenic effect of ASCs in mechanistic detail. We hypothesize that the miRNA-210 in hypoxia preconditioned ASCs-MVs is essential mediator of the proangiogenic effects of ASCs on angiogenesis. We will detect the proangiogenic efficacy of MVs from hypoxia preconditioned ASCs. Finally, we will examine the angiogenic effects of MVs from manipulated ASCs with down-regulation of miRNA-210 on hind limb ischemia. Consequently, modulation of composition in target cells by delivering angiogenic miRNA via preconditioned ASCs-released MVs would be an innovative strategy for the treatment of ischemic heart diseases.

脂肪干细胞因其易获得、增殖快等优点在血管再生医学治疗中引起了众多研究者的兴趣。然而，它促进血管再生的机制仍不清楚，旁分泌可能是其重要的机制，微泡作为细胞间相互沟通的新媒介成为旁分泌中的重要部分，它能传递mRNA和miRNA，在靶细胞中发挥促血管再生的作用。我们既往研究第一次说明，脂肪干细胞能分泌微泡，微泡可能促进血管再生，低氧预处理上调微泡分泌及微泡的促血管再生作用，并增加微泡中血管再生相关miR-210 水平。因此，我们假设微泡miR-210 在低氧培养脂肪干细胞旁分泌调节血管再生中发挥作用。我们拟检测低氧培养脂肪干细胞微泡是否促进血管再生，微泡miR-210 在促血管再生中是否发挥作用。如达到预期结果，能为微泡移植用于缺血性心脑血管疾病的治疗、为微泡作为miRNAs 新的传递载体用于临床提供一定的理论与实践基础。

脂肪干细胞因其易获得、增殖快等优点在血管再生医学治疗中引起了众多研究者的兴趣。然而，它促进血管再生的机制不清楚，旁分泌可能是其重要的机制，微泡作为细胞间相互沟通的新媒介成为旁分泌中的重要部分，它能传递mRNA和miRNA，在靶细胞中发挥促血管再生的作用。我们既往研究第一次说明，脂肪干细胞能分泌微泡，微泡可能促进血管再生，低氧预处理上调微泡分泌及微泡促血管再生作用，并增加微泡中血管再生相关miR-210水平。因此，我们假设微泡miR-210 在低氧培养脂肪干细胞旁分泌调节血管再生中发挥作用。我们拟检测低氧培养脂肪干细胞微泡是否促进血管再生，微泡miR-210 在促血管再生中是否发挥作用。如达到预期结果，能为微泡移植用于缺血性心脑血管疾病的治疗、为微泡作为miRNAs 新的传递载体用于临床提供一定的理论与实践基础。