title: Inner ear progenitor cells can be generated in vitro from human bone marrow mesenchymal stem cells.
abstract: OBJECTIVE
  Mouse mesenchymal stem cells (MSCs) can generate sensory neurons and produce inner ear hair cell-like cells. An equivalent source from humans is highly desirable, given their potential application in patient-specific regenerative therapies for deafness. In this study, we explored the ability of human MSCs (hMSCs) to differentiate into otic lineages.
  
  
  METHODS
  hMSCs were exposed to culture media conditioned by human fetal auditory stem cells.
  
  
  RESULTS
  Conditioned media induced the expression of otic progenitor markers PAX8, PAX2, GATA3 and SOX2. After 4 weeks, cells coexpressed ATOH1, MYO7A and POU4F3 (indicators of hair cell lineage) or neuronal markers NEUROG1, POU4F1 and NEFH. Inhibition of WNT signaling prevented differentiation into otic progenitors, while WNT activation partially phenocopied results seen with the conditioned media.
  
  
  CONCLUSIONS
  This study demonstrates that hMSCs can be driven to express key genes found in the otic lineages and thereby promotes their status as candidates for regenerative therapies for deafness.
authors.affiliation: Centre for Stem Cell Biology & Department of Biomedical Sciences, University of Sheffield, Alfred Denny Building, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Boddy
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Ricardo
authors.initials: R
authors.lastname: Romero-Guevara
authors.forename: Lucksy
authors.initials: L
authors.lastname: Kottam
authors.forename: Illaria
authors.initials: I
authors.lastname: Bellantuono
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Rivolta
mesh_terms: D000293:Adolescent; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D017077:Culture Media, Conditioned; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D060449:Wnt Signaling Pathway
chemical_list: D000943:Antigens, Differentiation; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins