Adenovector-mediated gene delivery to human umbilical cord mesenchymal stromal cells induces inner ear cell phenotype

Cell Reprogram. 2013 Feb;15(1):43-54. doi: 10.1089/cell.2011.0097.

Abstract

Hearing is one of our main sensory systems and having a hearing disorder can have a significant impact in an individual's quality of life. Sensory neural hearing loss (SNHL) is the most common form of hearing loss; it results from the degeneration of inner ear sensory hair cells and auditory neurons in the cochlea, cells that are terminally differentiated. Stem cell-and gene delivery-based strategies provide an opportunity for the replacement of these cells. In recent years, there has been an increasing interest in gene delivery to mesenchymal stem cells. In this study, we evaluated the potential of human umbilical cord mesenchymal stromal cells (hUCMSCs) as a possible source for regenerating inner ear hair cells. The expression of Atoh1 induced the differentiation of hUCMSCs into cells that resembled inner ear hair cells morphologically and immunocytochemically, evidenced by the expression of hair cell-specific markers. The results demonstrated for the first time that hUCMSCs can differentiate into hair cell-like cells, thus introducing a new potential tissue engineering and cell transplantation approach for the treatment of hearing loss.

Publication types

  • Clinical Trial

MeSH terms

  • Adenoviridae*
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Differentiation*
  • Cell- and Tissue-Based Therapy
  • Cells, Cultured
  • Female
  • Gene Expression / genetics
  • Genetic Therapy
  • Hair Cells, Auditory, Inner / cytology*
  • Hair Cells, Auditory, Inner / metabolism*
  • Hearing Loss / genetics
  • Hearing Loss / metabolism
  • Hearing Loss / therapy
  • Humans
  • Male
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Transduction, Genetic*
  • Umbilical Cord* / cytology
  • Umbilical Cord* / metabolism

Substances

  • ATOH1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors