Mesenchymal stem cells as a treatment for peripheral arterial disease: current status and potential impact of type II diabetes on their therapeutic efficacy.
Mesenchymal stem cells as a treatment for peripheral arterial disease: current status and potential impact of type II diabetes on their therapeutic efficacy.
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间充质干细胞作为外围动脉疾病的一种治疗方法：II型糖尿病对其治疗功效的当前状态和潜在影响。
DOI：
10.1007/s12015-013-9433-8
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发表时间：
2013-06
影响因子：
4.8
通讯作者：
Messina, Louis M.
中科院分区：
文献类型：
--
作者：
Yan, Jinglian;Tie, Guodong;Xu, Ting Yu;Cecchini, Katharine;Messina, Louis M.
间充质干细胞（MSC），由于其旁分泌，转分化和免疫抑制作用，持有作为外周动脉疾病的治疗很大的希望。糖尿病是外周动脉疾病的重要危险因素;然而，II型糖尿病如何影响MSC的治疗功能知之甚少。这篇综述总结了目前的临床前和临床研究，已进行，以确定骨髓间充质干细胞治疗外周动脉疾病的疗效。我们还介绍了我们实验室关于诱导后肢缺血后II型糖尿病对MSCs新血管形成治疗效果的影响的研究结果。在我们的研究中，我们记录了db/db小鼠中的实验性II型糖尿病通过促进其向脂肪细胞分化而损害MSC的治疗功能，同时限制其向内皮细胞分化。此外，II型糖尿病损害了MSC促进缺血后肢新生血管形成的能力。我们进一步表明，MSC功能和多能性的这些损害继发于db/db MSC中高胰岛素血症诱导的Nox 4依赖性氧化应激。如果人MSC显示出类似的氧化应激诱导的功能损伤，这些发现可能允许更大地利用MSC移植的潜力，特别是在糖尿病或其他心血管风险因素的情况下，以及通过在移植前逆转MSC的氧化应激提供治疗方法。
Mesenchymal stem cells (MSCs), due to their paracrine, transdifferentiation, and immunosuppressive effects, hold great promise as a therapy for peripheral arterial disease. Diabetes is an important risk factor for peripheral arterial disease; however, little is known of how type II diabetes affects the therapeutic function of MSCs. This review summarizes the current status of preclinical and clinical studies that have been performed to determine the efficacy of MSCs in the treatment of peripheral arterial disease. We also present findings from our laboratory regarding the impact of type II diabetes on the therapeutic efficacy of MSCs neovascularization after the induction of hindlimb ischemia. In our studies, we documented that experimental type II diabetes in db/db mice impaired MSCs’ therapeutic function by favoring their differentiation towards adipocytes, while limiting their differentiation towards endothelial cells. Moreover, type II diabetes impaired the capacity of MSCs to promote neovascularization in the ischemic hindlimb. We further showed that these impairments of MSC function and multipotency were secondary to hyperinsulinemia-induced, Nox4-dependent oxidant stress in db/db MSCs. Should human MSCs display similar oxidant stress-induced impairment of function, these findings might permit greater leverage of the potential of MSC transplantation, particularly in the setting of diabetes or other cardiovascular risk factors, as well as provide a therapeutic approach by reversing the oxidant stress of MSCs prior to transplantation.
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影响因子：
3.6
作者：
Hamou C;Callaghan MJ;Thangarajah H;Chang E;Chang EI;Grogan RH;Paterno J;Vial IN;Jazayeri L;Gurtner GC
通讯作者：
Gurtner GC
DOI：
10.1007/978-1-60761-999-4_21
发表时间：
2011
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Gong, Zhaodi;Niklason, Laura E
通讯作者：
Niklason, Laura E
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
DOI：
10.1161/atvbaha.111.231100
发表时间：
2011-10-01
影响因子：
8.7
作者：
Ishii, Masakazu;Shibata, Rei;Murohara, Toyoaki
通讯作者：
Murohara, Toyoaki
影响因子：
20.1
作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
通讯作者：
Hare JM