Netrin-1 with stem cells promote angiogenesis in limb ischemic rats

Background: Recent findings have elucidated that netrin-1 has ability of promoting angiogenesis besides the functions in nervous system. Autologous mesenchymal stem cells (MSCs) transplantation is now proved to be an effective method to treat peripheral arterial disease. However there are still many patients who cannot complete full treatments. Therefore it is necessary to improve the effectiveness. This study estimated the curative effects in chronic limb ischemia when MSCs allied with netrin-1. Materials and methods: Thirty-six rats were made into chronic limb ischemia models. They were randomly assigned to four groups, netrin-1 + MSCs group (treated with netrin-1 and MSCs derived from peripheral blood), MSCs group (treated with MSCs individually), netrin-1 group (treated with netrin-1 individually), and control group (treated with saline). Measurements of murine behaviors, vascular endothelial growth factor expression, and capillary density in ischemia limb were performed on days 7, 14, and 28 after treatments; measurements of contraction force in ischemia limb was performed on day 28 after treatments to compare differences among the groups. Results: Netrin-1 allied with MSCs significantly increased Tarlov score, vascular endothelial growth factor expression, capillary density, and muscular strength in ischemia limb. Conclusions: Netrin-1 allied with MSCs derived from peripheral blood significantly promoted angiogenesis in aged rats with chronic limb ischemia. It may be a promising method of treating peripheral arterial disease in the future. (C) 2014 Elsevier Inc. All rights reserved.