Our understanding of stem cell biology, especially in regards to its use for therapeutic cardiovascular regeneration, has continued at a staggering pace. Over the past few years, the identification of endogenous cardiac stem cells has raised the exciting possibility of harnessing these cells for cardiac repair. Recently, our laboratory has observed the existence of a cardiac progenitor cell population. These so termed cardiac side-population (CSP) cells, identified in adult hearts by their distinct Hoechst dye efflux pattern, represent a distinct cardiac progenitor cell population, capable of both biochemical and, more importantly, functional cardiomyogenic differentiation through a process mediated by coupling with adult cardiomyocytes. Moreover, after myocardial infarction (Ml), CSP cells are acutely depleted, and are restored through self-renewal of endogenous CSP cells and homing of extra-cardiac bone marrow-derived side population (BMSP) stem cells. Following homing to the injured hearts, BMSP adopt an immunophenotype similar to endogenous CSP cells. As such, utilizing a multidisciplinary approach of in-vitro and in-vivo methodologies, the main goal of this proposal is to delineate the signaling pathways regulating the proliferation and differentiation of CSP cells. Additionally, we will determine the functional significance of BMSP cell homing to injured myocardium, with the ultimate goal of harnessing these adult stem cells for physiologically significant cardiac regeneration.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL086967-05
Application #
8111799
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Adhikari, Bishow B
Project Start
2007-08-01
Project End
2012-10-31
Budget Start
2011-08-01
Budget End
2012-10-31
Support Year
5
Fiscal Year
2011
Total Cost
$430,000
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Fisch, Sudeshna; Liao, Ronglih; Hsiao, Li-Li et al. (2016) Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats. J Vis Exp :
Cheng, Hui-Wen; Fisch, Sudeshna; Cheng, Susan et al. (2014) Assessment of right ventricular structure and function in mouse model of pulmonary artery constriction by transthoracic echocardiography. J Vis Exp :e51041
Guan, Jian; Mishra, Shikha; Qiu, Yiling et al. (2014) Lysosomal dysfunction and impaired autophagy underlie the pathogenesis of amyloidogenic light chain-mediated cardiotoxicity. EMBO Mol Med 6:1493-507
Guan, Jian; Mishra, Shikha; Shi, Jianru et al. (2013) Stanniocalcin1 is a key mediator of amyloidogenic light chain induced cardiotoxicity. Basic Res Cardiol 108:378
Tsukamoto, Kosuke; Mani, D R; Shi, Jianru et al. (2013) Identification of apolipoprotein D as a cardioprotective gene using a mouse model of lethal atherosclerotic coronary artery disease. Proc Natl Acad Sci U S A 110:17023-8
Mishra, Shikha; Guan, Jian; Plovie, Eva et al. (2013) Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish. Am J Physiol Heart Circ Physiol 305:H95-103
Sereti, Konstantina-Ioanna; Oikonomopoulos, Angelos; Unno, Kazumasa et al. (2013) ATP-binding cassette G-subfamily transporter 2 regulates cell cycle progression and asymmetric division in mouse cardiac side population progenitor cells. Circ Res 112:27-34
Shi, Jianru; Jiang, Bingbing; Qiu, Yiling et al. (2013) PGC1? plays a critical role in TWEAK-induced cardiac dysfunction. PLoS One 8:e54054
Sereti, Konstantina-Ioanna; Oikonomopoulos, Angelos; Unno, Kazumasa et al. (2013) Methods to study the proliferation and differentiation of cardiac side population (CSP) cells. Methods Mol Biol 1036:95-106
Liao, Ronglih; Podesser, Bruno K; Lim, Chee Chew (2012) The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping. Am J Physiol Heart Circ Physiol 303:H156-67

Showing the most recent 10 out of 25 publications