Acta Pharmacologica Sinica 2005 Sep; 26 (9): 1069-1075; doi: 10.1111/j.1745-7254.2005.00168.x

 
Original Article
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Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs1
 

Chun-ling FAN, Ping-jin GAO, Zai-qian CHE, Jian-jun LIU, Jian WEI, Ding-liang ZHU2

Shanghai Key Laboratory of Vascular Biology, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Second Medical University and National Key Laboratory for Medical Genomics, Health Science Center, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China

 

Aim: To investigate the hypothesis that transplantation with expanded autologous endothelial progenitor cells (EPC) could enhance neovascularization.

Methods: Peripheral blood mononuclear cells (PB-MNC) isolated from New Zealand White rabbits were cultured in vitro. At d 7, the adherent cells were collected for autologous transplantation. Rabbits with severe unilateral hind limb ischemia were randomly assigned to receive phosphate-buffered saline or expanded EPC in phosphate-buffered saline, administered by intramuscular injection in 6 sites of the ischemic thigh at postoperative d 7. Neovascularization was monitored by using the calf blood pressure ratio to indicate tissue perfusion, digital subtraction angiography to identify collateral vessel development and histological analysis of capillary density in the ischemic limb at d 35 after surgery.

Results: Autologous EPC transplantation produced significant amelioration in ischemic hind limbs, as indicated by a greater calf blood pressure ratio (0.52±0.04 vs 0.42±0.05, P<0.01), angiographic score (1.44±0.06 vs 0.98±0.08, P<0.01) and capillary density in muscle (195.2±5.4/mm2 vs 169.4±6.4/mm2, P<0.05), than controls.


Conclusion:
Transplantation of autologous expanded EPC can promote neovascularization in ischemic hindlimbs.

 

Keywords: vascular endothelium; hindlimb; ischemia; physiologic neovascularization; stem cell transplantation

 
1 Project supported by grants from the National Key Program of Basic Research (No G2000056904), from the Shanghai Science and Technology Committee (No 1DJ14005), and from the Shanghai Higher Education Bureau (No 02BQ22).

2 Correspondence to Prof Ding-liang ZHU.
Phn 86-21-6437-0045, ext 610901.
Fax 86-21-5465-4498.
E-mail zhudingliang@sibs.ac.cn
Received 2005-01-27     Accepted 2005-04-27

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