Pretreatment of Diabetic Adipose-derived Stem Cells with mitoTEMPO Reverses their Defective Proangiogenic Function in Diabetic Mice with Critical Limb Ischemia

Cell Transplantation

Original Articles

Chengxiang Li¹  Genrui Chen¹  Youhu Chen¹  Shuai Zhao¹  Maosen Yang¹  Congye Li¹  Haokao Gao¹  Kun Lian²  Qin Wang³ 

[1] Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China;Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China;Both the authors contributed equally to this article.;Department of Pharmacogenomics, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China;Both the authors contributed equally to this article.;

关键词: ADSC;    ROS;    diabetic mice;    critical limb ischemia;   

DOI  :  10.1177/0963689719885076

 received in 2019-07-02, accepted in 2019-10-03,  发布年份 2019

来源: Sage Journals

【 摘 要 】

Adipose-derived stem cells (ADSCs) have the ability to migrate to injury sites and facilitate tissue repair by promoting angiogenesis. However, the therapeutic effect of ADSCs from patients with diabetes is impaired due to oxidative stress. Given that diabetes is a group of metabolic disorders and mitochondria are a major source of reactive oxygen species (ROS), it is possible that mitochondrial ROS plays an important role in the induction of diabetic ADSC (dADSC) dysfunction. ADSCs isolated from diabetic mice were treated with mitoTEMPO, a mitochondrial ROS scavenger, or TEMPO, a universal ROS scavenger, for three passages. The results showed that pretreatment with mitoTEMPO increased the proliferation, multidifferentiation potential, and the migration and proangiogenic capacities of dADSCs to levels similar to those of ADSCs from control mice, whereas pretreatment with TEMPO showed only minor effects. Mechanistically, mitoTEMPO pretreatment enhanced the mitochondrial antioxidant capacity of dADSCs, and knockdown of superoxide dismutase reduced the restored mitochondrial antioxidant capacity and attenuated the proangiogenic effects induced by mitoTEMPO pretreatment. In addition, mitoTEMPO pretreatment improved the survival of dADSCs in diabetic mice with critical limb ischemia, showing protective effects similar to those of control ADSCs. Pretreatment of dADSCs with mitoTEMPO decreased limb injury and improved angiogenesis in diabetic mice with critical limb ischemia. These findings suggested that short-term pretreatment of dADSCs with a mitochondrial ROS scavenger restored their normal functions, which may be an effective strategy for improving the therapeutic effects of ADSC-based therapies in patients with diabetes.

【 授权许可】

CC BY-NC   
© The Author(s) 2019

【 图 表 】

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