Abstract
The specific transformative steps that occur from the multipotent through the mature cardiomyocyte state are determined in large part by changes in gene expression. The exact differentiation and developmental programs are tightly regulated in a step-wise systematic fashion based on the influence of specific instigating and signaling factors. Crucial to the observed cell behavior and tissue specific phenotypic differences are alterations in the organization, translocation and expression of nuclear proteins during differentiation. The cardiomyogenic differentiation of Mesenchymal Stem Cells (MSCs) remains a precarious process. Transplanted MSCs must respond to endogenous signaling molecules involved in early embryonic cardiomyogenesis by activating the specific gene regulatory network required for successful cardiomyogenesis and transdifferentiation. To do that, transplanted MSCs would have to be genuinely reprogrammed genetically to become functional cardiac myocytes. A consideration of recent experimental findings suggests that Bone morphogenic protein (BMP-2/4), insulin-like growth factor (IGF-1) and fibroblast growth factor (FGF-2) in combination is a potent inducer of MSC cardiomyogenesis. The development of an optimum and reliable in vitro culture milieu for directing their cardiomyogenesis will provide an indispensable model system for molecular studies and genetic manipulation.
Highlights
Mesenchymal stem cells (MSCs) are a unique population of non-hematopoietic adult stem cells resident in the bone marrow and within various adult tissues
Irrespective of tissue source, MSCs are purified on the basis of their spindly fibroblast-like morphology, adherence to culture plates, and ability to differentiate into a number of different mesodermal lineages as well positively express a panel of surface markers (CD90, CD105, CD106, CD73, CD44, CD166, CD29, etc.) while remaining negative for markers of hematopoietic and endothelial precursors, lymphocytes and macrophages such as (CD45, CD31, CD34, CD11a, CD14, etc.) [1,2,3,4,5,7,8]
MSCs have far failed to achieve the level of differentiation synonymous with native ventricular cardiomyocytes, their ability to recapitulate the embryonic cardiac developmental pathway and gene program under the influence of these three growth factors (GFs) (BMP-2, FGF-2 and IGF-1) provides a reproducible in vitro model system for further mechanistic studies
Summary
Mesenchymal stem cells (MSCs) are a unique population of non-hematopoietic adult stem cells resident in the bone marrow and within various adult tissues. Irrespective of tissue source, MSCs are purified on the basis of their spindly fibroblast-like morphology, adherence to culture plates, and ability to differentiate into a number of different mesodermal lineages as well positively express a panel of surface markers (CD90, CD105, CD106, CD73, CD44, CD166, CD29, etc.) while remaining negative for markers of hematopoietic and endothelial precursors, lymphocytes and macrophages such as (CD45, CD31, CD34, CD11a, CD14, etc.) [1,2,3,4,5,7,8]. Their use in cellular cardiomyoplasty is extensively documented and studied [4,5,6,7]
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