Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes.
BACKGROUND
Bone marrow stromal cells (BMSCs) have the potential to differentiate into various cells and can transdifferentiate into myocytes if an appropriate cellular environment is provided. However, the molecular signals that underlie this process are not fully understood. In this study, we show that BMSC differentiation is dependent on communication with cells in their microenvironment.


RESULTS
BMSCs were isolated from green fluorescent protein (GFP)-transgenic mice and cocultured with myocytes in a ratio of 1:40. Myocytes were obtained from neonatal rat ventricles. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction. Before coculturing, the BMSCs were negative for alpha-actinin and exhibited a nucleus with many nucleoli. After 7-day coculture with myocytes, some BMSCs became alpha-actinin-positive and formed gap junctions with native myocytes. However, BMSCs separated from myocytes by a semipermeable membrane were still negative for alpha-actinin. Transdifferentiated myocytes from BMSCs were microdissected from cocultures by laser captured microdissection to determine the changes in gene expression. BMSCs cocultured with myocytes expressed mouse cardiac transcription factor GATA-4.


CONCLUSIONS
When cocultured with myocytes, BMSCs can transdifferentiate into cells with a cardiac phenotype. Differentiated myocytes express cardiac transcription factors GATA-4 and myocyte enhancer factor-2. The transdifferentiation processes rely on intercellular communication of BMSCs with myocytes.
Xu
Meifeng
M
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA.
Wani
Maqsood
M
Dai
Yan-Shan
YS
Wang
Jiang
J
Yan
Mei
M
Ayub
Ahmar
A
Ashraf
Muhammad
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D017154:Stromal Cells / Q000166:cytology / Q000648:ultrastructure; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors; D049452:Green Fluorescent Proteins