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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement
FASEB Journal, Volume 20, No. 6, Year 2006
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Description
We previously reported that intramyocardial injection of bone marrow-derived mesenchymal stem cells overexpressing Akt (Akt-MSCs) inhibits ventricular remodeling and restores cardiac function measured 2 wk after myocardial infarction. Here, we report that the functional improvement occurs in < 72 h. This early remarkable effect cannot be readily attributed to myocardial regeneration from the donor cells. Thus, we hypothesized that paracrine actions exerted by the cells through the release of soluble factors might be important mechanisms of tissue repair and functional improvement after injection of the Akt-MSCs. Indeed, in the current study we demonstrate that conditioned medium from hypoxic Akt-MSCs markedly inhibits hypoxia-induced apoptosis and triggers vigorous spontaneous contraction of adult rat cardiomyocytes in vitro. When injected into infarcted hearts, the Akt-MSC conditioned medium significantly limits infarct size and improves ventricular function relative to controls. Support to the paracrine hypothesis is provided by data showing that several genes, coding for factors (VEGF, FGF-2, HGF, IGF-I, and TB4) that are potential mediators of the effects exerted by the Akt-MSC conditioned medium, are significantly up-regulated in the Akt-MSCs, particularly in response to hypoxia. Taken together, our data support Akt-MSC-mediated paracrine mechanisms of myocardial protection and functional improvement. © FASEB.
Authors & Co-Authors
Gnecchi, Massimiliano
United States, Durham
Duke University Medical Center
United States, Boston
Harvard Medical School
Morello, F.
United States, Durham
Duke University Medical Center
United States, Boston
Harvard Medical School
Ingwall, Joanne S.
United States, Durham
Duke University Medical Center
Dzau, Victor J.
United States, Durham
Duke University Medical Center
United States, Boston
Harvard Medical School
Statistics
Citations: 1,023
Authors: 4
Affiliations: 3
Identifiers
Doi:
10.1096/fj.05-5211com
ISSN:
08926638
Research Areas
Cancer
Noncommunicable Diseases