L-carnitine Extends the Telomere Length of the Cardiac Differentiated CD117+- Expressing Stem Cells

Abstract

Stem cell-based therapy has emerged as an attractive method for regenerating and repairing the lost heart organ. On other hand, poor survival and maintenance of the cells transferred into the damaged heart tissue are broadly accepted as serious barriers to enhance the efficacy of the regenerative therapy. For this reason, external factors, such as antioxidants are used as a favorite strategy by the investigators to improve the cell survival and retention properties. Therefore, the present study was conducted to investigate the In -vitro effect of L-carnitine (LC) on the telomere length and human telomerase reverse transcriptase (hTERT) gene expression in the cardiac differentiated bone marrow resident CD117⁺ stem cells through Wnt3/β-catenin and ERK1/2 pathways. To do this, bone marrow resident CD117⁺ stem cells were enriched by the magnetic-activated cell sorting (MACS) method, and were differentiated to the cardiac cells in the absence (-LC) and presence of the LC (+LC). Also, characterization of the enriched c-kit⁺ cells was performed using the flow cytometry and immunocytochemistry. At the end of the treatment period, the cells were subjected to the real-time PCR technique along with western blotting assay for measurement of the telomere length and assessment of mRNA and protein, respectively. The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the hTERT gene expression in the cardiac differentiated CD117⁺ stem cells. In addition, a significant increase was observed in the mRNA and protein expression of Wnt3, β-catenin and ERK1/2 as key components of these pathways. It can be concluded that the LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the cardiac differentiated bone marrow resident CD117⁺ stem cells via Wnt3/β-catenin and ERK1/2 signaling pathway components.

Keywords: Bone marrow resident CD117(+)stem cells; Cardiac regeneration; Cell transplantation; L-carnitine; Telomere length; Wnt3/β-catenin and ERK1/2 signaling pathways.