Generation of inner ear sensory cells from bone marrow-derived human mesenchymal stem cells

Regen Med. 2012 Nov;7(6):769-83. doi: 10.2217/rme.12.65.

Abstract

Aim: Hearing loss is the most common sensory disorder in humans, its main cause being the loss of cochlear hair cells. We studied the potential of human mesenchymal stem cells (hMSCs) to differentiate towards hair cells and auditory neurons.

Materials & methods: hMSCs were first differentiated to neural progenitors and subsequently to hair cell- or auditory neuron-like cells using in vitro culture methods.

Results: Differentiation of hMSCs to an intermediate neural progenitor stage was critical for obtaining inner ear sensory lineages. hMSCs generated hair cell-like cells only when neural progenitors derived from nonadherent hMSC cultures grown in serum-free medium were exposed to EGF and retinoic acid. Auditory neuron-like cells were obtained when treated with retinoic acid, and in the presence of defined growth factor combinations containing Sonic Hedgehog.

Conclusion: The results show the potential of hMSCs to give rise to inner ear sensory cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Antineoplastic Agents / pharmacology
  • Cell Differentiation*
  • Cells, Cultured
  • Chick Embryo
  • Ear, Inner* / cytology
  • Ear, Inner* / metabolism
  • Epidermal Growth Factor / pharmacology
  • Hair Cells, Auditory* / cytology
  • Hair Cells, Auditory* / metabolism
  • Hedgehog Proteins / pharmacology
  • Humans
  • Mesenchymal Stem Cells*
  • Neural Stem Cells*
  • Neurons / cytology
  • Neurons / metabolism
  • Tretinoin / pharmacology

Substances

  • Antigens, Differentiation
  • Antineoplastic Agents
  • Hedgehog Proteins
  • SHH protein, human
  • Tretinoin
  • Epidermal Growth Factor