INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

Improvement of cardiac function in mouse myocardial infarction after transplantation of epigenetically-modified bone marrow progenitor cells

Show simple item record

Bookmark or cite this item: http://hdl.handle.net/10027/8573

Files in this item

File Description Format
PDF journal.pone.0022550.pdf (5MB) (no description provided) PDF
Title: Improvement of cardiac function in mouse myocardial infarction after transplantation of epigenetically-modified bone marrow progenitor cells
Author(s): Rajasingh, Johnson; Thangavel, Jayakumar; Siddiqui, Mohammad R.; Gomes, Ignatius; Gao, Xiao-pei; Kishore, Raj; Malik, Asrar B.
Subject(s): epigenetic bone marrow progenitor
Abstract: 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.
Issue Date: 2011-07-22
Publisher: Public Library of Science
Citation Info: Rajasingh, J., Thangavel, J., Siddiqui, M. R., Gomes, I., Gao, X. P., Kishore, R., & Malik, A. B. 2011. Improvement of cardiac function in mouse myocardial infarction after transplantation of epigenetically-modified bone marrow progenitor cells. PLoS One, 6(7): e22550. DOI: 10.1371/journal.pone.0022550.
Type: Article
Description: © 2011 Rajasingh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.1371/journal.pone.0022550.
URI: http://hdl.handle.net/10027/8573
ISSN: 1932-6203
Sponsor: This work was supported, in part, by American Heart Association Grant - Jon Holden DeHaan Foundation 10SDG2630181 and National Institutes of Health (NIH) grant R21HL97349 (to JR) and RO1HL90152 (to ABM).
Date Available in INDIGO: 2012-08-20
 

This item appears in the following Collection(s)

Show simple item record

Statistics

Country Code Views
United States of America 133
China 16
United Kingdom 13
Germany 2
Netherlands 2

Browse

My Account

Information

Access Key