[Neovascularization potential of mobilized peripheral mononuclear cells from diabetes patients].
OBJECTIVE
To determine whether mobilized peripheral blood mononuclear cells (M-PBMNCs) obtained from patients with diabetes was impaired in therapeutic neovascularization in limb ischemia, and to explore the pathological mechanisms of the impairment.


METHODS
Endothelial progenitor cells (EPC) were cultured in EGM-2MV, and then characterized by uptake of 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindocarbocyanine-labeled acetylated low density lipoprotein (Dil-AcLDL) and binding of ulex europaeus agglutinin (UEA). The number of EPC was compared between M-PBMNCs obtained from diabetic patients and those from normal subjects. M-PBMNCs obtained from diabetic patients, M-PBMNCs obtained from normal controls, or PBS were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion was detected by laser Doppler blood perfusion imaging between these three groups in the following 1, 3, 7, 14, 21, and 28 days. Ambulatory score and ischemia damage were evaluated in the following 4 weeks. Capillary/fiber ratio was detected by CD31 or BS-1 lectin, and arteriole density was detected by alpha-smooth muscle actin (alpha-SMactin).


RESULTS
The number of EPC from diabetic patients were positively correlated with the blood perfusion (R = 0.486, P < 0.05) and capillary density (R = 0.491, P < 0.05), and the EPC number in diabetic patient were negatively correlation with their disease courses (R = - 0.587, P < 0.05). Transplantation of diabetic M-PBMNCs augmented the blood perfusion of ischemia hindlimbs, increased the capillary and arteriole densities, and promoted the collateral vessel formation. However, all the improvements were less significant in the diabetic patients than in the non-diabetic patients (P < 0.05).


CONCLUSIONS
Diabetes decreased the capability of M-PBMNCs to augment neovascularization in ischemia.
Zhou
Bin
B
National Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering and Technology, Institute of Hematology, CAMS and PUMC, Tianjin 300020, China.
Gu
Dong-Sheng
DS
Liu
Peng-Xia
PX
Zheng
Cui-Ling
CL
Dong
Chun-Lan
CL
Du
Wei-Ting
WT
Wu
Kai-Hong
KH
Han
Zhong-Chao
ZC
D000818:Animals; D003920:Diabetes Mellitus / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation; D005121:Extremities / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000502:physiology* / Q000637:transplantation; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation