PMID- 15492307
OWN - NLM
STAT- MEDLINE
DCOM- 20050512
LR  - 20071114
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 110
IP  - 17
DP  - 2004 Oct 26
TI  - Differentiation of bone marrow stromal cells into the cardiac phenotype requires 
      intercellular communication with myocytes.
PG  - 2658-65
AB  - 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 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.
FAU - Xu, Meifeng
AU  - Xu M
AD  - Department of Pathology and Laboratory Medicine, University of Cincinnati Medical 
      Center, Cincinnati, OH, USA.
FAU - Wani, Maqsood
AU  - Wani M
FAU - Dai, Yan-Shan
AU  - Dai YS
FAU - Wang, Jiang
AU  - Wang J
FAU - Yan, Mei
AU  - Yan M
FAU - Ayub, Ahmar
AU  - Ayub A
FAU - Ashraf, Muhammad
AU  - Ashraf M
LA  - eng
GR  - HL074272/HL/NHLBI NIH HHS/United States
GR  - HL70062/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041018
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Transcription Factors)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*cytology
MH  - *Cell Communication
MH  - Cell Differentiation
MH  - Coculture Techniques
MH  - Green Fluorescent Proteins/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocytes, Cardiac/*cytology/metabolism/ultrastructure
MH  - Phenotype
MH  - Stromal Cells/cytology/ultrastructure
MH  - Transcription Factors/metabolism
EDAT- 2004/10/20 09:00
MHDA- 2005/05/13 09:00
CRDT- 2004/10/20 09:00
PHST- 2004/10/20 09:00 [pubmed]
PHST- 2005/05/13 09:00 [medline]
PHST- 2004/10/20 09:00 [entrez]
AID - 01.CIR.0000145609.20435.36 [pii]
AID - 10.1161/01.CIR.0000145609.20435.36 [doi]
PST - ppublish
SO  - Circulation. 2004 Oct 26;110(17):2658-65. doi: 
      10.1161/01.CIR.0000145609.20435.36. Epub 2004 Oct 18.