Apelin 13: A novel approach to enhance efficacy of hypoxic preconditioned mesenchymal stem cells for cell therapy of diabetes

Apelin 13: A novel approach to enhance efficacy of hypoxic preconditioned mesenchymal stem cells for cell therapy of diabetes
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DOI:
10.1016/j.mehy.2012.08.007
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发表时间:
2012-12-01
期刊:
影响因子:
4.7
通讯作者:
Sharifi, Ali M.
Sharifi, Ali M.
中科院分区:
医学4区
文献类型:
--
作者:
Mottaghi, S.;Larijani, B.;Sharifi, Ali M.

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最近的研究已经提出细胞治疗作为许多疾病状态的替代治疗策略,如糖尿病。在不同的细胞类型中,间充质干细胞(MSC)因其令人感兴趣的潜力而引起了人们的极大关注。然而,由于大部分移植细胞在移植后发生凋亡,MSC治疗受到限制。因此,提出一个克服这一障碍的策略可能是很有价值的。最近的研究表明,缺氧预处理(HPC)可以提高移植后的细胞活力。据报道,HPC和高血糖都通过不同水平的ROS过量产生而发挥作用。在这种情况下,过量的ROS会引发细胞凋亡,从而降低移植后的细胞活力。组织Apelin;G蛋白偶联受体APJ的内源性配体通过MAPK/ERK1/2和PI3K/AKT信号通路在MSCs氧化应激诱导的凋亡中发挥抗凋亡作用。因此,我们假设用apelin 13预处理HPC-MSCs将是一种有效的方法,可以修饰并可能增强MSCs在糖尿病细胞治疗中的疗效。(C) 2012 Elsevier Ltd.版权所有。
Recent studies have proposed cell therapy as an alternative therapeutic strategy for many disease states such as diabetes mellitus. Among different cell types mesenchymal stem cells (MSC) have attracted a significant attention based on their intriguing potentials. However MSC therapy is limited as a large portion of transplanted cells undergo apoptosis after transplantation. Therefore, proposing a strategy to overcome this obstacle may be of great value. Recent studies have shown that hypoxia preconditioning (HPC) may improve cell viability after transplantation. Both HPC and hyperglycemia are reported to exert effects by different levels of ROS overproduction. Overdose of ROS in this case would trigger the apoptosis and thereby decreased cell viability after transplantation. Apelin; the endogenous ligand for the previously orphaned G protein-coupled receptor APJ is shown to exert anti apoptotic effects On oxidative stress-induced apoptosis in MSCs via MAPK/ERK1/2 and PI3K/AKT signaling pathways. Accordingly it has been hypothesized that pretreatment of HPC-MSCs with apelin 13 would be an effective approach to modify and possibly enhance the efficacy of MSCs in cell therapy of diabetes. (C) 2012 Elsevier Ltd. All rights reserved.