Cell-Based Therapy Restores Olfactory Function in an Inducible Model of Hyposmia

Sarah Kurtenbach, Garrett M. Goss, Stefania Goncalves, Rhea Choi, Joshua M. Hare, Nirupa Chaudhari, Bradley J. Goldstein

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Stem cell-based therapies have been proposed as a strategy to replace damaged tissues, especially in the nervous system. A primary sensory modality, olfaction, is impaired in 12% of the US population, but lacks treatment options. We report here the development of a novel mouse model of inducible hyposmia and demonstrate that purified tissue-specific stem cells delivered intranasally engraft to produce olfactory neurons, achieving recovery of function. Adult mice were rendered hyposmic by conditional deletion of the ciliopathy-related IFT88 gene in the olfactory sensory neuron lineage and following experimentally induced olfactory injury, received either vehicle or stem cell infusion intranasally. Engraftment-derived olfactory neurons were identified histologically, and functional improvements were measured via electrophysiology and behavioral assay. We further explored mechanisms in culture that promote expansion of engraftment-competent adult olfactory basal progenitor cells. These findings provide a basis for translational research on propagating adult tissue-specific sensory progenitor cells and testing their therapeutic potential. Olfactory sensory losses lack treatment options. The corresponding author and colleagues report the testing of a cellular therapy for olfactory loss. Inducible hyposmia was produced by targeting ciliopathy to the olfactory lineage in mice, and wild-type adult stem cells engrafted to produce functional neurons, assessed using histology, electrophysiology, and behavioral assay.

Original languageEnglish (US)
Pages (from-to)1354-1365
Number of pages12
JournalStem Cell Reports
Volume12
Issue number6
DOIs
StatePublished - Jun 11 2019

Keywords

  • anosmia
  • ciliopathy
  • neuron
  • olfaction
  • stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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