Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes

Meifeng Xu, Maqsood Wani, Yan Shan Dai, Jiang Wang, Mei Yan, Ahmar Ayub, Muhammad Ashraf

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)2658-2665
Number of pages8
JournalCirculation
Volume110
Issue number17
DOIs
StatePublished - Oct 26 2004

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Mesenchymal Stromal Cells
Muscle Cells
Phenotype
Actinin
GATA4 Transcription Factor
Coculture Techniques
MEF2 Transcription Factors
Microdissection
Gap Junctions
Green Fluorescent Proteins
Cardiac Myocytes
Cell Communication
Transgenic Mice
Reverse Transcription
Cell Differentiation
Electron Microscopy
Lasers
Immunohistochemistry
Gene Expression
Polymerase Chain Reaction

Keywords

  • Genetics
  • Myocytes
  • Signal transduction
  • Stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes. / Xu, Meifeng; Wani, Maqsood; Dai, Yan Shan; Wang, Jiang; Yan, Mei; Ayub, Ahmar; Ashraf, Muhammad.

In: Circulation, Vol. 110, No. 17, 26.10.2004, p. 2658-2665.

Research output: Contribution to journalArticle

Xu, Meifeng ; Wani, Maqsood ; Dai, Yan Shan ; Wang, Jiang ; Yan, Mei ; Ayub, Ahmar ; Ashraf, Muhammad. / Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes. In: Circulation. 2004 ; Vol. 110, No. 17. pp. 2658-2665.
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AU - Ayub, Ahmar

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N2 - 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 α-actinin and exhibited a nucleus with many nucleoli. After 7-day coculture with myocytes, some BMSCs became α-actinin-positive and formed gap junctions with native myocytes. However, BMSCs separated from myocytes by a semipermeable membrane were still negative for α-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.

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