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Engraftment of Human Stem Cell-Derived Otic Progenitors in the Damaged Cochlea

Alejandra Lopez-Juarez1, Hanae Lahlou2, Chantal Ripoll3

  • 1CNRS UMR 7260, Aix-Marseille Université, Marseille, France; Chemical, Electronic and Biomedical Engineering, Universidad de Guanajuato, Guanajuato, Mexico.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|April 22, 2019
PubMed

Insights

Human otic progenitor cells (hOPCs) derived from induced pluripotent stem cells (iPSCs) successfully engrafted and survived in a guinea pig model of sensorineural deafness. These cells showed potential for sensory differentiation, offering hope for new hearing loss treatments.

Area of Science:

  • Regenerative Medicine
  • Otolaryngology
  • Stem Cell Biology

Background:

  • Sensorineural deafness often results from hair cell degeneration.
  • Stem cell therapy shows promise for organ regeneration, but cochlear engraftment remains unproven.
  • Developing effective cell-based treatments for hearing loss requires demonstrating successful cell survival and integration in the cochlea.

Purpose of the Study:

  • To generate human otic progenitor cells (hOPCs) from induced pluripotent stem cells (iPSCs).
  • To assess the in vivo survival, migration, and differentiation potential of iPSC-derived hOPCs in an adult mammalian cochlea.
  • To establish proof-of-concept for stem cell therapy in treating sensorineural deafness.

Main Methods:

  • Generated hOPCs from iPSCs in vitro, identified by otic markers.
  • Transplanted iPSC-derived hOPCs into an adult guinea pig model of ototoxicity.
  • Utilized Atoh1-GFP mouse hair cell progenitors to confirm findings in a similar delivery system.

Main Results:

  • Transplanted hOPCs successfully engrafted in non-sensory cochlear regions and survived for up to 4 weeks.
  • Engrafted hOPCs responded to cochlear environmental cues, exhibiting early sensory differentiation markers.
  • Mouse otic progenitors also migrated into damaged cochlear epithelium and adopted partial sensory cell fates.

Conclusions:

  • This study demonstrates the first successful survival and differentiation of human otic progenitor cells in an injured mature cochlear environment.
  • These findings support the potential of iPSC-derived hOPCs for cell-based therapies aimed at treating sensorineural deafness.
  • Further research into stem cell therapies is warranted to advance treatments for hearing loss.
Keywords:
animal model of ototoxicitycell injection assayengraftmenthuman induced pluripotent cellsin vitro otic modelmigrationotic progenitor cellssensory cell differentiationtransplantation

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