Yong-Li Wang1, Guitao Zhang2, Hai-Jie Wang3, Yu-Zhen Tan4, Xin-Yan Wang1. 1. Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China. 2. Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China; Department of Anatomy, Histology and Embryology, Capital Medical University, Beijing, China. 3. Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China. Electronic address: hjwang@shmu.edu.cn. 4. Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China. Electronic address: yztan@shmu.edu.cn.
Abstract
BACKGROUND: Preclinical and clinical trails show that c-kit+ cardiac stem cells can differentiate towards cardiovascular cells and improve cardiac function after myocardial infarction (MI). However, survival and differentiation of the engrafted stem cells within ischemic and inflammatory microenvironment are poor. METHODS: c-Kit+ cells were isolated from mesenchymal stem cells (MSCs) of rat bone marrow. Reliability of preinduction with bone morphogenetic protein-2 (BMP-2) in promotion of survival and differentiation of c-kit+ MSCs was assessed in vitro and after transplantation. RESULTS: c-Kit+ MSCs have a potential to differentiate towards cardiomyocytes. BMP-2 promotes proliferation, migration and paracrine of the cells, and protects the cells to survive in the hypoxic condition. After induction with 10 ng/mL BMP-2 for 24 h, the cells can differentiate into cardiomyocytes at four weeks. The electrophysiological characteristics of the differentiated cells are same as adult ventricular cardiomyocytes. In rat MI models, cardiac function was improved, the size of scar tissue was reduced, and regeneration of the myocardium and microvessels was enhanced significantly at four weeks after transplantation of BMP-2-preinduced cells. The survived cells and cardiomyocytes differentiated from the engrafted cells were increased greatly. CONCLUSION: The results suggest that transient treatment with BMP-2 can induce c-kit+ MSCs to differentiate into functional cardiomyocytes. Preinduction with BMP-2 enhances survival and differentiation of the cells. BMP-2-primed cells promote repair of the infarcted myocardium and improvement of cardiac function. Transplantation of BMP-2-preinduced c-kit+ MSCs is a feasible strategy for MI therapy.
BACKGROUND: Preclinical and clinical trails show that c-kit+ cardiac stem cells can differentiate towards cardiovascular cells and improve cardiac function after myocardial infarction (MI). However, survival and differentiation of the engrafted stem cells within ischemic and inflammatory microenvironment are poor. METHODS: c-Kit+ cells were isolated from mesenchymal stem cells (MSCs) of rat bone marrow. Reliability of preinduction with bone morphogenetic protein-2 (BMP-2) in promotion of survival and differentiation of c-kit+ MSCs was assessed in vitro and after transplantation. RESULTS: c-Kit+ MSCs have a potential to differentiate towards cardiomyocytes. BMP-2 promotes proliferation, migration and paracrine of the cells, and protects the cells to survive in the hypoxic condition. After induction with 10 ng/mL BMP-2 for 24 h, the cells can differentiate into cardiomyocytes at four weeks. The electrophysiological characteristics of the differentiated cells are same as adult ventricular cardiomyocytes. In rat MI models, cardiac function was improved, the size of scar tissue was reduced, and regeneration of the myocardium and microvessels was enhanced significantly at four weeks after transplantation of BMP-2-preinduced cells. The survived cells and cardiomyocytes differentiated from the engrafted cells were increased greatly. CONCLUSION: The results suggest that transient treatment with BMP-2 can induce c-kit+ MSCs to differentiate into functional cardiomyocytes. Preinduction with BMP-2 enhances survival and differentiation of the cells. BMP-2-primed cells promote repair of the infarcted myocardium and improvement of cardiac function. Transplantation of BMP-2-preinduced c-kit+ MSCs is a feasible strategy for MI therapy.