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

1 Citation (Scopus)

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

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Cell- and Tissue-Based Therapy
Stem cells
Neurons
Stem Cells
Electrophysiology
Tissue
Assays
Histology
Olfactory Receptor Neurons
Neurology
Testing
Adult Stem Cells
Translational Medical Research
Smell
Recovery of Function
Therapeutics
Genes
Nervous System
Recovery
Wounds and Injuries

Keywords

  • anosmia
  • ciliopathy
  • neuron
  • olfaction
  • stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Cell-Based Therapy Restores Olfactory Function in an Inducible Model of Hyposmia. / Kurtenbach, Sarah; Goss, Garrett M.; Goncalves, Stefania; Choi, Rhea; Hare, Joshua M.; Chaudhari, Nirupa; Goldstein, Bradley J.

In: Stem Cell Reports, Vol. 12, No. 6, 11.06.2019, p. 1354-1365.

Research output: Contribution to journalArticle

Kurtenbach, Sarah ; Goss, Garrett M. ; Goncalves, Stefania ; Choi, Rhea ; Hare, Joshua M. ; Chaudhari, Nirupa ; Goldstein, Bradley J. / Cell-Based Therapy Restores Olfactory Function in an Inducible Model of Hyposmia. In: Stem Cell Reports. 2019 ; Vol. 12, No. 6. pp. 1354-1365.
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