L-Carnitine Promotes Cardiomyogenic Differentiation of C-Kit+Bone Marrow Progenitor Cells via MAPK-ERK Signaling Pathway

Abstract

Many studies have shown that bone marrow (BM) stem/progenitor cells have the highest probability of cardiomyocyte differentiation. Regarding the major role of C-kit⁺ BM stem cells in cell therapy of patients with heart disease and getting cells with higher differentiation potential, this study aimed to investigate the capacity and effect of L-carnitine (LC) on cardiomyogenic differentiation of C-kit⁺ BM cells through MAPK/ERK signaling pathway. For this purpose, C-kit⁺ was enriched from the BM mononuclear cell population using a magnetic activating cell sorting technique. The purity of the separated C-kit⁺ cells was then evaluated by flow cytometry. In the next step, C-Kit⁺ cells were treated in a cardiomyogenic differentiation culture medium for 21 days once in the presence and once in the absence of 0.2 µM LC (the experimental and control groups). To evaluate the cardiomyogenic differentiation potential of C-kit⁺ cells, the Desmin cell marker was determined by immunocytochemistry. The expressions of both GATA4 and ERK proteins were measured using western blotting and flow cytometry, respectively. The results show that 95.7 percent of the cells separated by the MACS technique expressed a C-kit⁺ cell marker. Additionally, it was found that 0.2 mM LC significantly increased the expression of GATA4 protein in the cardiomyogenic differentiated cells. The expression of ERK protein also suggested a significant increase of about 1.60 times in the experimental group in comparison with the control group (*P˂0.05). In brief, it was found that treating C-kit⁺ BM cells with LC increases cardiomyogenic differentiation by increasing the expression of GATA4. Notably, this effect can take place through MARK/ERK signaling pathway. The results of this research can be valuable in suggesting a treatment solution for cardiovascular diseases.