Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells  

作　　者：Bin ZHOU Xiao-cang CAO Zhi-hong FANG Cui-lin ZHENG Zhi-bo HAN He REN Man-chiu POON Zhong-chao HAN 

机构地区：[1]State Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering and Technology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China [2]Department Gastroenterology, TMU, General Hopital of Tianjin Medical University, Tianjin 300052, China [3]Departments of Medicine, University of Calgary, Alberta T2N 2T9, Canada

出　　处：《Acta Pharmacologica Sinica》2007年第1期89-97,共9页中国药理学报（英文版）

基　　金：Project supported by grants of 863(No 2003AA205060);National Major Grants for Basic Research(No 001CB5101)from the Ministry of Science and Technology of China.

摘　　要：Aim： To investigate whether the prophylactic local delivery of mobilized peripheral blood mononuclear cells （M-PBMNC） could prevent peripheral microangiopathy in diabetic nude mice. Methods： Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immuno- histopathy. In situ apoptosis was detected by using TdT-mediated dUTP nick end labeling （TUNEL） methods. M-PBMNC were labeled and locally delivered to the adductor muscles. Mononuclear cells were also isolated and cultured in vitro for the detection and counting of endothelial progenitor cells（EPC）. Results： Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles, and reduced circulating EPC in diabetic nude mice. Prophylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skeletal muscles by inhibiting apoptosis. We detected the survival, migration and incorporation of transplanted M-PBMNC into the murine vasculature in vivo. In addition, more EPC were available from M-PBMNC than non-mobilized cells. Conclusion： These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.Aim： To investigate whether the prophylactic local delivery of mobilized peripheral blood mononuclear cells （M-PBMNC） could prevent peripheral microangiopathy in diabetic nude mice. Methods： Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immuno- histopathy. In situ apoptosis was detected by using TdT-mediated dUTP nick end labeling （TUNEL） methods. M-PBMNC were labeled and locally delivered to the adductor muscles. Mononuclear cells were also isolated and cultured in vitro for the detection and counting of endothelial progenitor cells（EPC）. Results： Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles, and reduced circulating EPC in diabetic nude mice. Prophylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skeletal muscles by inhibiting apoptosis. We detected the survival, migration and incorporation of transplanted M-PBMNC into the murine vasculature in vivo. In addition, more EPC were available from M-PBMNC than non-mobilized cells. Conclusion： These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.

关 键 词：PREVENTION diabetic angiopathis TRANSPLANTATION endothelial cells stem cells 

分 类 号：R587.1[医药卫生—内分泌]