vitamin C enhances cardiac cells production via partial reprogramming of mouse fibroblasts

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 288

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شناسه ملی سند علمی:

WTRMED06_104

تاریخ نمایه سازی: 5 بهمن 1398

چکیده مقاله:

Heart diseases are the most significant cause of morbidity and mortality in the world. Cell therapy has been proposed as a promising approach to treat the cardiac diseases. Pluripotent stem cells have been focused as a reliable source for producing cardiomyocytes, and many attempts have been done for efficient production of cardiomyocytes. There are some challenges regarding pluripotent stem cell derived cardiomyocytes, which are cardiomyocyte isolation and purification, maturity and survival and integration after transplantation to heart. The newest method to produce cardiomyocyte is transdifferentiation from fibroblasts, which is a rapid, simple and safe aprochoch to generate cardiomyocyte in vitro and in vivo. In the present study, mouse fibroblast were transdifferetiated to beating cardiac cells following epigenetic instability establishment in the fibroblasts. Epigenetic instability was induced by temporarily overexpression of pluripotency related transcription factors (OSKM). In order to promote the direct cardiac conversion, 10 candidate small molecules were added to the cells and the efficiency of beating patch formation was analyzed. Through this screening, ascorbic acid (AA) was identified to promote direct cardiac conversion up to 13-fold and its promoting effect was further increased by BMP4. Immunostaining and gene expression analysis for pluripotency and cardiac lineage markers showed that the beating patches were derived from non-cardiac lineage cells without passing the fully pluripotent state. Further examination revealed that AA also increased the size of beating area and the number of cardiac progenitor cells (CPC). Immunostaining for cardiac markers and electrophysiological analysis confirmed the functionality of direct converted cardiomyocytes. These results illustrate the importance of AA in direct conversion of fibroblasts to cardiomyocytes and may open new way for cardiomyocyte generation required in cardiac cell therapy.

نویسندگان

Mahmood Talkhabi

Ph.D, student of STEM CELLS, Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran