Dynamics of human myocardial progenitor cell Populations in the neonatal period

Stanford University, Palo Alto, California, United States
The Annals of thoracic surgery (Impact Factor: 3.65). 11/2008; 86(4):1311-9. DOI: 10.1016/j.athoracsur.2008.06.058
Source: PubMed

ABSTRACT Pluripotent cardiac progenitor cells resident in myocardium offer a potentially promising role in promoting recovery from injury. In pediatric congenital heart disease (CHD) patients, manipulation of resident progenitor cells may provide important new approaches to improving outcomes. Our study goals were to identify and quantitate populations of progenitor cells in human neonatal myocardium during the early postnatal period and determine the proliferative capacity of differentiated cardiac myocytes.
Immunologic markers of cell lineage (stage-specific embryonic antigen 4 [SSEA-4], islet cell antigen 1 [Isl1], c-kit, Nkx2.5, sarcoplasmic reticulum calcium-regulated ATPase type 2 [SERCA2]) and proliferation (Ki67) were localized in right ventricular biopsies from 32 CHD patients aged 2 to 93 days.
Neonatal myocardium contains progenitor cells and transitional cells expressing progenitor and differentiated myocyte marker proteins. Some cells expressed the pluripotent cell marker c-kit and also coexpressed the myocyte marker SERCA2. Multipotent progenitor cells, identified by the expression of Isl1, were found. Ki67 was expressed in some myocytes and in nonmyocyte cells. A few cells expressing SSEA-4 and Isl1 were observed during the early postnatal period. Cells expressing c-kit, the premyocyte marker Nkx2.5, and Ki67 were found throughout the first postnatal month. A progressive decline in cell density during the first postnatal month was observed for c-kit+ cells (p = 0.0013) and Nkx2.5+ cells (p = 0.0001). The percentage of cells expressing Ki67 declined during the first 3 postnatal months (p = 0.0030).
Cells in an incomplete state of cardiomyocyte differentiation continue to reside in the infant heart. However, the relative density of progenitor cells declines during the first postnatal month.

Download full-text


Available from: Robert Kirk Riemer, Oct 06, 2014
  • Revue Neurologique 04/2007; 163(4):170-170. DOI:10.1016/S0035-3787(07)90821-8 · 0.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past decade, cell therapy has emerged as a potential new treatment of a variety of cardiac diseases, including acute myocardial infarction, refractory angina, and chronic heart failure. A myriad of cell types have been tested experimentally, each of them being usually credited by its advocates of a high "regeneration" potential. This has led to a flurry of clinical trials entailing the use of skeletal myoblasts or bone marrow-derived cells either unfractionated or enriched in progenitor subpopulations. As often in medicine, the hype generated by the early uncontrolled and small-sized studies has been dampened by the marginally successful outcomes of the subsequent, more rigorously conducted randomized trials. Although they may have failed to achieve their primary end points, these trials have been positive in the sense that they have allowed to identify some key issues and it is reasonable to speculate that if these issues can now be addressed by appropriately focused benchwork, the outcomes of the second generation of cell-transplantation studies would likely be upgraded. It, thus, appears that not "one cell fits all" but that the selection of the cell type should be tailored to the primary clinical indication. On the one hand, it does not make sense to develop an "ideal" cell in a culture dish, if we remain unable to deliver it appropriately and to keep it alive, at least for a while, which requires to improve on the delivery techniques and to provide cells along with the vascular and extracellular matrix type of support necessary for their survival and patterning. On the other hand, the persisting mechanistic uncertainties about cell therapy should not preclude continuing clinical trials, which often provide the unique opportunity of identifying issues missed by our suboptimal preclinical models. Finally, regardless of whether cells are expected to act paracrinally or by physically replacing lost cardiomyocytes and, thus, effecting a true myocardial regeneration, safety remains a primary concern. It is, thus, important that clinical development programs be shaped in a way that allows the final cell-therapy product to be manufactured from fully traceable materials, phenotypically well characterized, consistent, scalable, sterile, and genetically stable as these characteristics are those that will be required by the ultimate gatekeeper, i.e., the regulator, and are thus unbypassable prerequisites for an effective and streamlined leap from bench to bedside.
    Molecular Therapy 04/2009; 17(5):758-66. DOI:10.1038/mt.2009.40 · 6.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Influencing cellular regeneration processes in the heart has been a long-standing goal in cardiovascular medicine. To some extent, this has been successful in terms of vascular regeneration as well as intercellular connective tissue remodeling processes. Several components of today's routine heart failure medication influence endothelial progenitor cell behavior and support collateral vessel growth in the heart, or have been shown to prevent or reverse fibrosis processes. Cardiomyocyte regeneration, however, has so far escaped therapeutic manipulation strategies. Delivery of exogenous cells of bone marrow origin to the human myocardium may improve heart function, but is not associated with relevant neomyogenesis. However, accumulating evidence indicates that the myocardium contains resident cardiac progenitor cells (CPC) that may be therapeutically useful. This notion indeed represents a paradigm shift but is still controversial. The purpose of this review is to summarize the rapidly expanding current knowledge on CPC, and to assess whether it may be translated into solid therapeutic concepts.
    Therapeutic Advances in Cardiovascular Disease 06/2009; 3(3):215-29. DOI:10.1177/1753944709336190 · 2.13 Impact Factor