Su Guan-Hua, Sun Yu-Fei, Lu Yong-Xin, Shuai Xin-Xin, Liao Yu-Hua, Liu Qi-Yun, Han Jun, Luo Ping
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.
J Huazhong Univ Sci Technolog Med Sci. 2013 Aug;33(4):511-519. doi: 10.1007/s11596-013-1151-6. Epub 2013 Aug 1.
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.
目前，针对外周动脉疾病（PAD）的血管生成基因治疗和基于细胞的治疗已得到深入研究。本研究旨在探讨在大鼠后肢缺血模型中，间充质干细胞（MSCs）移植与体外人肝细胞生长因子（HGF）基因转导相结合是否比单独的MSCs治疗具有更高的治疗效率。建立后肢缺血模型一周后，将Sprague-Dawley（SD）大鼠随机分为三组，分别接受HGF基因修饰的MSCs移植（HGF-MSC组）、未处理的MSCs移植（MSC组）或PBS注射（PBS组）。注射三周后，MSCs和HGF-MSCs移植均显著诱导了血管生成，且HGF-MSC组的毛细血管密度最高。治疗一周后，HGF-MSC组移植细胞来源的内皮细胞数量多于MSC组。局部缺血肌肉中HGF和VEGF等血管生成细胞因子的表达在HGF-MSC组中比其他两组更丰富。在体外，从HGF-MSCs培养物中获得的条件培养基对内皮细胞具有促增殖和促迁移作用。结论是，HGF基因修饰的MSCs移植治疗可能比单独的MSCs治疗诱导更有效的血管生成。MSCs移植与血管生成基因递送相结合可能是治疗重度PAD的一种有前景的治疗策略。
