Bone marrow mesenchymal stem cells are progenitors in vitro for inner ear hair cells.
Stem cells have been demonstrated in the inner ear but they do not spontaneously divide to replace damaged sensory cells. Mesenchymal stem cells (MSC) from bone marrow have been reported to differentiate into multiple lineages including neurons, and we therefore asked whether MSCs could generate sensory cells. Overexpression of the prosensory transcription factor, Math1, in sensory epithelial precursor cells induced expression of myosin VIIa, espin, Brn3c, p27Kip, and jagged2, indicating differentiation to inner ear sensory cells. Some of the cells displayed F-actin positive protrusions in the morphology characteristic of hair cell stereociliary bundles. Hair cell markers were also induced by culture of mouse MSC-derived cells in contact with embryonic chick inner ear cells, and this induction was not due to a cell fusion event, because the chick hair cells could be identified with a chick-specific antibody and chick and mouse antigens were never found in the same cell.
Jeon
Sang-Jun
SJ
Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA.
Oshima
Kazuo
K
Heller
Stefan
S
Edge
Albert S B
AS
D000199:Actins / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D002923:Cilia / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D018920:Coculture Techniques; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D000199:Actins; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C500943:Atoh1 protein, mouse