Hepatocyte Growth Factor Gene-modified Bone Marrow-derived Mesenchymal Stem Cells Transplantation Promotes Angiogenesis in a Rat Model of Hindlimb Ischemia

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 4; pp. 511 - 519
• Main Authors: Su, Guan-hua, Sun, Yu-fei, Lu, Yong-xin, Shuai, Xin-xin, Liao, Yu-hua, Liu, Qi-yun, Han, Jun, Luo, Ping
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2013; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China%Department of Cardiology, Wuhan Pu'ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
• Subjects: Animals; Bone Marrow - metabolism; Bone Marrow - pathology; Bone Marrow Transplantation; Cells, Cultured; Hepatocyte Growth Factor - genetics; Hindlimb - pathology; Medicine; Medicine & Public Health; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Neovascularization, Physiologic - genetics; Rats; Sprague-Dawley; 基因修饰; 大鼠模型; 干细胞移植; 缺血; 肝细胞生长因子; 血管新生; 骨髓间充质干细胞; mesenchymal stem cell; gene therapy; peripheral arterial disease; angiogenesis; hepatocyte growth factor
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1151-6

Summary： Angiogenic gene therapy and cell-based therapy for peripheral arterial disease （PAD） have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells （MSCs）transplantation with ex vivo human hepatocyte growth factor （HGF） gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley （SD） rats were randomized to receive HGF gene-modified MSCs transplantation （HGF-MSC group）, untreated MSCs transplantation （MSC group）, or PBS injection （PBS group）, respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.