Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Critical Limb Ischemia in Diabetic Nude Rats

Cell Transplantation

Article

Youwei Wang¹  Zongjin Li¹  Tao Ma²  Lu Liang²  Zhong Chao Han³  Meng Zhao⁴  Lanzhen Zhao⁴  Jimin Wang⁴  Bingjing Zhang⁴  Honghong Jia⁴  Jie Feng⁴  Jie Geng⁴  Alain Rupin⁵  Zhibo Han⁶  Wenjing Du⁶ 

[1] Beijing Institute of Stem Cells, Health & Biotech Co., Beijing, P.R. China;Beijing Institute of Stem Cells, Health & Biotech Co., Beijing, P.R. China; National Engineering Research Center of Cell Products, Tianjin, P.R. China;Beijing Institute of Stem Cells, Health & Biotech Co., Beijing, P.R. China; National Engineering Research Center of Cell Products, Tianjin, P.R. China; State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, P.R. China;National Engineering Research Center of Cell Products, Tianjin, P.R. China;Servier Phamaceutical Co., Ltd., Suresnes, France;State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, P.R. China;

关键词: Placenta-derived mesenchymal stem cells (P-MSCs);    Critical limb ischemia (CLI);    Angiogenesis;    Cell therapy;   

DOI  :  10.3727/096368916X692726

 received in 2016-02-29, accepted in 2016-10-14,  发布年份 2017

来源: Sage Journals

【 摘 要 】

Neovasculogenesis induced by stem cell therapy is an innovative approach to improve critical limb ischemia (CLI) in diabetes. Mesenchymal stem cells (MSCs) are ideal candidates due to their angiogenic and immunomodulatory features. The aim of this study is to determine the therapeutic effects of human placenta-derived MSCs (P-MSCs) on diabetic CLI, with or without exogenous insulin administration, and the underlying mechanism of any effect. A series of in vitro experiments were performed to assess the stemness and vasculogenic activity of P-MSCs. P-MSCs were intramuscularly injected at two different doses with and without the administration of insulin. The efficacy of P-MSC transplantation was evaluated by ischemia damage score, ambulatory score, laser Doppler perfusion image (LDPI), capillary, and vascular density. In vivo imaging was applied to track the implanted P-MSCs. In vivo differentiation and in situ secretion of angiogenic cytokines were determined. In vitro experimental outcomes showed the differentiation potential and potent paracrine effect of P-MSCs. P-MSCs survived in vivo for at least 3 weeks and led to the acceleration of ischemia recovery, due to newly formed capillaries, increased arterioles, and secretion of various proangiogenic factors. P-MSCs participate in angiogenesis and vascularization directly through differentiation and cytokine expression.

【 授权许可】

Unknown   
© 2017 SAGE Publications Inc

【 图 表 】

Figure 4.