Article

Developmental and regenerative biology of multipotent cardiovascular progenitor cells.

CPZN 3224 Simches Building, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114, USA.
Circulation Research (Impact Factor: 11.09). 02/2011; 108(3):353-64. DOI: 10.1161/CIRCRESAHA.110.227066
Source: PubMed

ABSTRACT Our limited ability to improve the survival of patients with heart failure is attributable, in part, to the inability of the mammalian heart to meaningfully regenerate itself. The recent identification of distinct families of multipotent cardiovascular progenitor cells from endogenous, as well as exogenous, sources, such as embryonic and induced pluripotent stem cells, has raised much hope that therapeutic manipulation of these cells may lead to regression of many forms of cardiovascular disease. Although the exact source and cell type remains to be clarified, our greater understanding of the scientific underpinning behind developmental cardiovascular progenitor cell biology has helped to clarify the origin and properties of diverse cells with putative cardiogenic potential. In this review, we highlight recent advances in the understanding of cardiovascular progenitor cell biology from embryogenesis to adulthood and their implications for therapeutic cardiac regeneration. We believe that a detailed understanding of cardiogenesis will inform future applications of cardiovascular progenitor cells in heart failure therapy and regenerative medicine.

0 Bookmarks
 · 
103 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The devastating impact of congenital heart defects has made mechanisms of vertebrate heart and vascular development an active area of study. Because myocyte death is a common feature of acquired cardiovascular diseases and the adult heart does not regenerate, the need exists to understand whether features of the developing heart and vasculature—which are more plastic—can be exploited therapeutically in the disease setting. We know that a core network of transcription factors governs commitment to the cardiovascular lineage, and recent studies using genetic loss-of-function approaches and unbiased genomic studies have revealed the role for various chromatin modulatory events. We reason that chromatin structure itself is a causal feature that influences transcriptome complexity along a developmental continuum, and the purpose of this article is to highlight the areas in which ‘omics technologies have the potential to reveal new principles of phenotypic plasticity in development. We review the major mechanisms of chromatin structural regulation, highlighting what is known about their actions to control cardiovascular differentiation. We discuss emergent mechanisms of regulation that have been identified on the basis of genomic and proteomic studies of cardiac nuclei and identify current challenges to an integrated understanding of chromatin structure and cardiovascular phenotype.This article is protected by copyright. All rights reserved
    Proteomics 07/2014; · 3.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Stem cell therapy has a potential for regenerating damaged myocardium. However, a key obstacle to cell therapy's success is the loss of engrafted cells due to apoptosis or necrosis in the ischemic myocardium. While many strategies have been developed to improve engrafted cell survival, tools to evaluate cell efficacy within the body are limited. Traditional genetic labeling tools, such as GFP-like fluorescent proteins (eGFP, DsRed, mCherry), have limited penetration depths in vivo due to tissue scattering and absorption. To circumvent these limitations, a near-infrared fluorescent mutant of the DrBphP bacteriophytochrome from Deinococcus radiodurans, IFP1.4, was developed for in vivo imaging, but it has yet to be used for in vivo stem/progenitor cell tracking. In this study, we incorporated IFP1.4 into mouse cardiac progenitor cells (CPCs) by a lentiviral vector. Live IFP1.4-labeled CPCs were imaged by their near-infrared fluorescence (NIRF) using an Odyssey scanner following overnight incubation with biliverdin. A significant linear correlation was observed between the amount of cells and NIRF signal intensity in in vitro studies. Lentiviral mediated IFP1.4 gene labeling is stable, and does not impact the apoptosis and cardiac differentiation of CPC. To assess efficacy of our model for engrafted cells in vivo, IFP1.4-labeled CPCs were intramyocardially injected into infarcted hearts. NIRF signals were collected at 1-day, 7-days, and 14-days post-injection using the Kodak in vivo multispectral imaging system. Strong NIRF signals from engrafted cells were imaged 1 day after injection. At 1 week after injection, 70% of the NIRF signal was lost when compared to the intensity of the day 1 signal. The data collected 2 weeks following transplantation showed an 88% decrease when compared to day 1. Our studies have shown that IFP1.4 gene labeling can be used to track the viability of transplanted cells in vivo.
    PLoS ONE 10/2014; 9(10):e107841. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: microRNAs are post-transcriptional regulators of gene expression that have been shown to be central players in the establishment of cellular programs, often acting as switches that control the choice between proliferation and differentiation during development and in adult tissues. The heart develops from two small patches of cells in the mesoderm, the heart fields, which originate the different cardiac cell types, including cardiomyocytes, vascular smooth muscle and endothelial cells. These progenitors proliferate and differentiate to establish a highly connected three-dimensional structure, involving a robust succession of gene expression programs strongly influenced by microRNAs. Although the mammalian heart has conventionally been viewed as a post-mitotic organ, cardiac cells have recently been shown to display some regenerative potential, which is nonetheless insufficient to regenerate heart lesions, in contrast with other vertebrates like the zebrafish. Both the proliferation of adult cardiac stem cells and the ability of cardiomyocytes to re-enter the cell cycle have been proposed to sustain these regenerative processes. Here we review the role of microRNAs in the control of stem cell and cardiomyocyte dependent cardiac regeneration processes, and discuss potential applications for the treatment of cardiac injury.
    Cells. 12/2014; 3(4):996-1026.

Preview

Download
1 Download
Available from