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.Stem cells resident in bone marrow are the source of blood cells, but in addition to these hematopoietic stem cells, the bone marrow contains mesenchymal stem cells (MSCs) that can differentiate into cell types of all three embryonic germ layers (Colter et al., 2000;Doyonnas et al., 2004;Herzog et al., 2003;Hess et al., 2003;Jiang et al., 2002;Pittenger et al., 1999). This has been demonstrated in vivo in studies that track transplanted bone marrow cells to specific tissues where they differentiate into the resident tissue type (Mezey et al., 2003;Weimann et al., 2003). Differentiation may occur in part due to cell fusion (Wang et al., 2003;Weimann et al., 2003) in which the bone marrow cell takes on the identity of the peripheral cell. Recent studies have documented ex vivo differentiation of bone marrow derived stem cells into muscle cells (Doyonnas et al., 2004), cartilage (Pittenger et al., 1999), insulin-producing cells (Hess et al., 2003), and neurons (Dezawa et al., 2004;Hermann et al., 2004;Jiang et al., 2003;Kicic et al., 2003), both in vitro and after injection of these cells in vivo. Many of these cells have been used for transplantation and are a © 2006 Elsevier Inc. All rights reserved.Corresponding author: Albert Edge Eaton-Peabody Laboratory Massachusetts Eye and Ear Infirmary 243 Charles Street Boston, MA 02114 Tel: (617) 573-4452 Fax: (617) 720-4408 albert_edge@meei.harvard.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptMol Cell Neurosci. Author manuscript; available in PMC 2011 July 14. (Satoh and Fekete, 2005), and by the effect on hair ce...

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