PMID- 19544423
OWN - NLM
STAT- MEDLINE
DCOM- 20100113
LR  - 20151119
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 27
IP  - 8
DP  - 2009 Aug
TI  - c-Kit function is necessary for in vitro myogenic differentiation of bone marrow 
      hematopoietic cells.
PG  - 1911-20
LID - 10.1002/stem.106 [doi]
AB  - In recent years, the differentiation of bone marrow cells (BMCs) into myocytes 
      has been extensively investigated, but the findings remain inconclusive. The 
      purpose of this study was to determine the conditions necessary to induce 
      myogenic differentiation in short-term cultures of adult BMCs, and to identify 
      the BMC subpopulation responsible for this phenomenon. We report that 
      high-density cultures of murine hematopoietic BMCs gave rise to spontaneous 
      beating cell clusters in the presence of vascular endothelial and fibroblast 
      growth factors. These clusters originated from c-kit(pos) cells. The formation of 
      the clusters could be completely blocked by adding a c-kit/tyrosine kinase 
      inhibitor, Gleevec (imatinib mesylate; Novartis International, Basel, 
      Switzerland, http://www.novartis.com), to the culture. Cluster formation was also 
      blunted in BMCs from c-kit-deficient (Kit(W)/Kit(W-v)) mice. Clustered cells 
      expressed cardiomyocyte-specific transcription factor genes Gata-4 and Nkx2.5, 
      sarcomeric proteins beta-MHC and MLC-2v, and ANF and connexin-43. Immunostaining 
      revealed alpha-sarcomeric actinin expression in more than 90% of clustered cells. 
      Under electron microscopy, the clustered cells exhibited a sarcomeric myofiber 
      arrangement and z-bands. This study defines the microenvironment required to 
      achieve a reproducible in vitro model of beating, myogenic cell clusters. This 
      model could be used to examine the mechanisms responsible for the postnatal 
      myogenic differentiation of BMCs. Our results identify c-kit(pos) bone marrow 
      hematopoietic cells as the source of the myogenic clusters.
FAU - Xaymardan, Munira
AU  - Xaymardan M
AD  - Division of Cardiovascular Surgery, Toronto General Research Institute, 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Cimini, Massimo
AU  - Cimini M
FAU - Fazel, Shafie
AU  - Fazel S
FAU - Weisel, Richard D
AU  - Weisel RD
FAU - Lu, Wei-Yang
AU  - Lu WY
FAU - Martin, Ulrich
AU  - Martin U
FAU - Harvey, Richard P
AU  - Harvey RP
FAU - Li, Ren-Ke
AU  - Li RK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Benzamides
MH  - Bone Marrow Cells/*cytology/drug effects/metabolism
MH  - Cell Differentiation/physiology
MH  - Cell Lineage
MH  - Cell Movement/physiology
MH  - Cells, Cultured
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Gene Expression
MH  - Hematopoietic Stem Cells/*cytology/drug effects/metabolism
MH  - Humans
MH  - Imatinib Mesylate
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microscopy, Electron
MH  - Microscopy, Phase-Contrast
MH  - Myocytes, Cardiac/cytology/metabolism
MH  - Piperazines/pharmacology
MH  - Proto-Oncogene Proteins c-kit/*metabolism
MH  - Pyrimidines/pharmacology
MH  - Vascular Endothelial Growth Factor A/pharmacology
EDAT- 2009/06/23 09:00
MHDA- 2010/01/14 06:00
CRDT- 2009/06/23 09:00
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2010/01/14 06:00 [medline]
AID - 10.1002/stem.106 [doi]
PST - ppublish
SO  - Stem Cells. 2009 Aug;27(8):1911-20. doi: 10.1002/stem.106.