Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model

Background. Bone marrow possesses endothelial progenitor cells that secrete several growth factors and can contribute to the formation of new capillar ies. In the present study, we investigated the extent of angiogenesis induc ed by implantation of autologous bone marrow cells (BMCs) in a rat ischemic hindlimb model and studied whether the increased collateral vessels can im prove deteriorated physical function. Materials and methods. Ischemic hindlimb was created by ligation of the fem oral artery and its branches in Dark Agouti (DA) rats. BMCs (1 x 10(7)) wer e injected percutaneously at six points into the gastrocnemius muscle. To a ssess angiogenesis, histologic evaluation and microangiography were perform ed at 2 weeks postligation. Severity of the ischemic insult was evaluated b y measuring blood flow in the adductor and gastrocnemius muscles using nonr adioactive colored microspheres and by determining the femoral arteriovenou s oxygen difference (AVDO(2)) at 2 weeks postligation. Running time on a mo tor-driven treadmill was used to represent exercise capacity. Results. The histologic evaluation and microangiogram showed that the impla nted BMCs induce angiogenesis. Blood flow to the adductor muscle on the tre ated side in the bone marrow cell implantation (BMI) group was significantl y restored to 77.3 +/- 19.3% of that of the normally perfused limb in compa rison to that in control groups (P < 0.05). AVDO(2) in the BMI group signif icantly decreased when compared with AVDO(2) in control groups. Rats in the BMI group ran approximately 1.5 times longer than rats in control groups a t 2 and 4 weeks postligation (P < 0.01). Conclusions. Implantation of autologous BMCs induced angiogenesis and impro ved deteriorated exercise capacity in our rat ischemic hindlimb model. (C) 2001 Academic Press.