Format

Send to

Choose Destination
Stem Cell Reports. 2019 Jun 11;12(6):1354-1365. doi: 10.1016/j.stemcr.2019.05.001. Epub 2019 May 30.

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

Author information

1
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.
2
Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
3
Medical Scientist Training Program, 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.
4
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 Medicine, Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
5
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; Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
6
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: b.goldstein4@med.miami.edu.

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

PMID:
31155504
DOI:
10.1016/j.stemcr.2019.05.001
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center