Published Online
on October 18, 2004

A more recent version of this article appeared on October 26, 2004

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Submitted on December 30, 2003
Revised on June 1, 2004
Accepted on June 3, 2004

Differentiation of Bone Marrow Stromal Cells Into the Cardiac Phenotype Requires Intercellular Communication With Myocytes

Meifeng Xu MD, PhD, Maqsood Wani PhD, Yan-Shan Dai MD, PhD, Jiang Wang MD, PhD, Mei Yan MD, PhD, Ahmar Ayub DVM, and Muhammad Ashraf PhD^*

From the Department of Pathology and Laboratory Medicine (M.X., J.W., M.Y., A.A., M.A.), University of Cincinnati Medical Center, and the Department of Pediatrics (M.W., Y.-S.D.), University of Cincinnati, Children’s Hospital Medical Center, Cincinnati, Ohio.

^* To whom correspondence should be addressed. E-mail: Muhammad.Ashraf{at}uc.edu.

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.

Methods and 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 -actinin and exhibited a nucleus with many nucleoli. After 7-day coculture with myocytes, some BMSCs became -actinin-positive and formed gap junctions with native myocytes. However, BMSCs separated from myocytes by a semipermeable membrane were still negative for -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.

Key words: myocytes • stem cells • signal transduction • genetics

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