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

Affiliation

Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, Biomedical Research Building, Room 809, Miami, FL 33136, USA; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Graduate Program in Neurosciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: [Email]

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.

Keywords

anosmia,ciliopathy,neuron,olfaction,stem cells,

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