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


CONCLUSIONS
These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.
Zhou
Bin
B
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.
Cao
Xiao-Cang
XC
Fang
Zhi-Hong
ZH
Zheng
Cui-Lin
CL
Han
Zhi-Bo
ZB
Ren
He
H
Poon
Man-Chiu
MC
Han
Zhong-Chao
ZC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D042783:Endothelial Cells / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000637:transplantation*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control
D016179:Granulocyte Colony-Stimulating Factor