Improvement of Cardiac Function in Mouse Myocardial Infarction after Transplantation of Epigenetically-Modified Bone Marrow Progenitor CellsReportar como inadecuado




Improvement of Cardiac Function in Mouse Myocardial Infarction after Transplantation of Epigenetically-Modified Bone Marrow Progenitor Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Objective

To study usefulness of bone marrow progenitor cells BPCs epigenetically altered by chromatin modifying agents in mediating heart repair after myocardial infarction in mice.

Methods and Results

We tested the therapeutic efficacy of bone marrow progenitor cells treated with the clinically-used chromatin modifying agents Trichostatin A TSA, histone deacetylase inhibitor and 5Aza-2-deoxycytidine Aza, DNA methylation inhibitor in a mouse model of acute myocardial infarction AMI. Treatment of BPCs with Aza and TSA induced expression of pluripotent genes Oct4, Nanog, Sox2, and thereafter culturing these cells in defined cardiac myocyte-conditioned medium resulted in their differentiation into cardiomyocyte progenitors and subsequently into cardiac myocytes. Their transition was deduced by expression of repertoire of markers: Nkx2.5, GATA4, cardiotroponin T, cardiotroponin I, α-sarcomeric actinin, Mef2c and MHC-α. We observed that the modified BPCs had greater AceH3K9 expression and reduced histone deacetylase1 HDAC1 and lysine-specific demethylase1 LSD1 expression compared to untreated BPCs, characteristic of epigenetic changes. Intra-myocardial injection of modified BPCs after AMI in mice significantly improved left ventricular function. These changes were ascribed to differentiation of the injected cells into cardiomyocytes and endothelial cells.

Conclusion

Treatment of BPCs with Aza and TSA converts BPCs into multipotent cells, which can then be differentiated into myocyte progenitors. Transplantation of these modified progenitor cells into infarcted mouse hearts improved left ventricular function secondary to differentiation of cells in the niche into myocytes and endothelial cells.



Autor: Johnson Rajasingh , Jayakumar Thangavel, Mohammad R. Siddiqui, Ignatius Gomes, Xiao-pei Gao, Raj Kishore, Asrar B. Malik

Fuente: http://plos.srce.hr/



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