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infarction, is the leading cause of death worldwide. The most common cause of heart failure is
acute myocardial infarction (AMI). AMI leads to a series of cellular events: apoptosis, necrosis
reduced contractility; and pathological remodeling. Most therapeutic methods focus on reducing
early mortality by regulating hemodynamics, rather than tissue regeneration to facilitate cardiac
repair to avoid heart failure. Mesenchymal stem cells (MSCs) have provided considerable
promise in regenerative therapy. In preclinical studies using MSCs for AMI, improved cardiac
function was observed. However, in animal studies, administered MSCs showed low (~2%)
transplantation. Therefore, it was unlikely that the observed improvement in cardiac function
resulted from the contribution of MSCs to replenish cardiomyocte populations, but is instead a
factors secreted by MSCs are collectively known as the MSC secretome. A typical MSC
secretion profile consists of growth factors, cytokines, extracellular matrix proteases, hormones,
and lipid mediators. In human MSC analysis, 132 unique proteins were identified using Liquid
Chromatography with Tandem Mass Spectrometry Detection and 72 using antibody arrays.
While current techniques have been able to identify factors expressed at high levels, a complete
list of expressed secretome factors is yet to be generated. Recent studies have suggested potential
MSC transdifferentiation into contractile cardiomyocytes is inefficient and only occurs in the
presence of native cardiomyocytes. Strong evidence also suggests that rat-derived MSCs secrete
trophic factors that induce activation and proliferation of cardiac progenitor cells in vitro,
although these progenitor cells possess only a limited capacity to differentiate into fully mature
cardiomyocytes with an adult phenotype. The most plausible explanation for MSC-mediated
cardiovascular repair is an effect on the host cells and its microenvironment due to its secreted
growth factors, cytokines, and other signaling molecules. MSCs are sources of
immunomodulatory agents and trophic factors involved in repair and regenerative processes.
MSCs through paracrine signaling and have antiapoptotic, anti-inflammatory, and antifibrotic
inflammation and pathological remodeling. Transplanted MSCs are often short-lived, thus,
physiological, genetic, molecular, and pharmacological strategies are utilized to extend MSC
survival and improve response to highly dynamic signaling cues during myocardial infarction.
Available trial results are not as promising due to the use of nonoptimized MSC formulations and
improve homing, survival, and secretome control the is currently favored approach for regulating
cells. In addition, clarification of the underlying signaling pathways should develop more
effect.
Reference:
Ranganath, S., Levy, O., Inamdar, M., & Karp, J. (2012). Harnessing the Mesenchymal Stem
Cell Secretome for the Treatment of Cardiovascular Disease. Cell Stem Cell, 10(3), 244-258.
doi:10.1016/j.stem.2012.02.005