A Common Progenitor at the Heart of Development

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell (Impact Factor: 32.24). 01/2007; 127(6):1101-4. DOI: 10.1016/j.cell.2006.11.031
Source: PubMed


Formation of the heart requires the coordinated functions of cardiac myocytes, smooth muscle cells, endothelial cells, and connective tissue elements. Several recent studies now reveal that these different cell types arise from a common progenitor (Kattman et al., 2006; Moretti et al., 2006; Wu et al., 2006). These findings raise interesting questions about the lineage relationships of cardiovascular progenitor cell populations and suggest possibilities for cardiac repair in both congenital and acquired heart disease.

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    • "The only exception to this was coronary artery endothelial cells, which clustered with other cardiac cells. This is consistent with current knowledge, which suggests a common epicardial origin for all cardiac cells [21]. Notably endothelial cells did not cluster with cells from similar segmental regions, suggesting a hierarchy of endothelial identities unrelated to an “organ specific” identity. "
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    ABSTRACT: The endothelial cell has a remarkable ability for sub-specialisation, adapted to the needs of a variety of vascular beds. The role of developmental programming versus the tissue contextual environment for this specialization is not well understood. Here we describe a hierarchy of expression of HOX genes associated with endothelial cell origin and location. In initial microarray studies, differential gene expression was examined in two endothelial cell lines: blood derived outgrowth endothelial cells (BOECs) and pulmonary artery endothelial cells. This suggested shared and differential patterns of HOX gene expression between the two endothelial lines. For example, this included a cluster on chromosome 2 of HOXD1, HOXD3, HOXD4, HOXD8 and HOXD9 that was expressed at a higher level in BOECs. Quantative PCR confirmed the higher expression of these HOXs in BOECs, a pattern that was shared by a variety of microvascular endothelial cell lines. Subsequently, we analysed publically available microarrays from a variety of adult cell and tissue types using the whole "HOX transcriptome" of all 39 HOX genes. Using hierarchical clustering analysis the HOX transcriptome was able to discriminate endothelial cells from 61 diverse human cell lines of various origins. In a separate publically available microarray dataset of 53 human endothelial cell lines, the HOX transcriptome additionally organized endothelial cells related to their organ or tissue of origin. Human tissue staining for HOXD8 and HOXD9 confirmed endothelial expression and also supported increased microvascular expression of these HOXs. Together these observations suggest a significant involvement of HOX genes in endothelial cell positional identity.
    PLoS ONE 03/2014; 9(3):e91334. DOI:10.1371/journal.pone.0091334 · 3.23 Impact Factor
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    • "Embryonic stem cells (ESCs), described on humans by Thompson [27] are the prototypical stem cells. They unambiguously fulfill all requirements of stem cells: clonality, self renewal and multipotentiality [28]. ES are able to differentiate into any adult cells and can efficiently generate both functional beating mature CMCs and vasculature; however, their therapeutic use is hampered by associated teratoma formation and the need for an allogeneic source [29]. "
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    ABSTRACT: Although the adult mammalian heart was once believed to be a post-mitotic organ without any capacity for regeneration, recent findings have challenged this dogma. A modified view assigns to the mammalian heart a measurable capacity for regeneration throughout life. The ultimate goals of the cardiac regeneration field have been pursued by multiple strategies, including understanding the developmental biology of cardiomyocytes and cardiac stem and progenitor cells, applying chemical genetics, and engineering biomaterials and delivery methods that facilitate cell transplantation. Successful stimulation of endogenous regenerative capacity in injured adult mammalian hearts can benefit from studies of natural cardiac regeneration.
    Stem cell reviews 08/2013; 9(6). DOI:10.1007/s12015-013-9461-4 · 2.77 Impact Factor
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    • "Epicardial precursor cells with the ability to differentiate into cardiomyocytes and vascular cells have been identified challenging the quiescence of adult epicardial cells [36]. These cells seem to originate from the same cells as the multipotent cardiovascular progenitors of the heart and play a role in the process of cardiomyogenesis and vasculogenesis in the developing myocardium [37]. Overall there is an emerging role of resident cardiac stem cells or progenitor cells as well as epicardial cells as promising targets in the therapy of heart failure [38]. "
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    ABSTRACT: Mammalian myocardium has a finite but limited capacity to regenerate. Experimentally stimulating proliferation of cardiomyocytes with extracellular regeneration factors like periostin enhances cardiac repair in rodents. The aim of this study was to develop a safe method for delivering regeneration factors to the heart and to test the functional and structural effects of periostin peptide treatment in a large animal model of myocardial infarction (MI). We developed a controlled release system to deliver recombinant periostin peptide into the pericardial space. A single application of this method was performed two days after experimental MI in swine. Animals were randomly assigned to receive either saline or periostin peptide. Experimental groups were compared at baseline, day 2, 1 month and 3 months. Treatment with periostin peptide increased the EF from 31% to 41% and decreased by 22% the infarct size within 12 weeks. Periostin peptide-treated animals had newly formed myocardium strips within the infarct scar, leading to locally improved myocardial function. In addition the capillary density was increased in animals receiving periostin. However, periostin peptide treatment increased myocardial fibrosis in the remote region at one week and 12 weeks post-treatment. Our study shows that myocardial regeneration through targeted peptides is possible. However, in the case of periostin the effects on cardiac fibrosis may limit its clinical application as a viable therapeutic strategy.
    PLoS ONE 05/2013; 8(5):e59656. DOI:10.1371/journal.pone.0059656 · 3.23 Impact Factor
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