Olfactory Regeneration with Nasally Administered Murine Adipose-Derived Stem Cells in Olfactory Epithelium Damaged Mice

Tomoko Ishikura; Hideaki Shiga; Yuka Nakamura; Takako Kanitani; Yasuhito Ishigaki; Takaki Miwa

doi:10.3390/cells12050765

Olfactory Regeneration with Nasally Administered Murine Adipose-Derived Stem Cells in Olfactory Epithelium Damaged Mice

Cells. 2023 Feb 27;12(5):765. doi: 10.3390/cells12050765.

Authors

Tomoko Ishikura¹, Hideaki Shiga¹, Yuka Nakamura², Takako Kanitani¹, Yasuhito Ishigaki^{2

3}, Takaki Miwa¹

Affiliations

¹ Department of Otorhinolaryngology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
² Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
³ Center for Regenerative Medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan.

Abstract

In this study, we aimed to determine whether nasally administered murine adipose-derived stem cells (ADSCs) could support olfactory regeneration in vivo. Olfactory epithelium damage was induced in 8-week-old C57BL/6J male mice by intraperitoneal injection of methimazole. Seven days later, OriCell adipose-derived mesenchymal stem cells obtained from green fluorescent protein (GFP) transgenic C57BL/6 mice were nasally administered to the left nostril of these mice, and their innate odor aversion behavior to butyric acid was assessed. Mice showed significant recovery of odor aversion behavior, along with improved olfactory marker protein (OMP) expression on both sides of the upper-middle part of the nasal septal epithelium assessed by immunohistochemical staining 14 d after the treatment with ADSCs compared with vehicle control animals. Nerve growth factor (NGF) was detected in the ADSC culture supernatant, NGF was increased in the nasal epithelium of mice, and GFP-positive cells were observed on the surface of the left side nasal epithelium 24 h after left side nasal administration of ADSCs. The results of this study suggest that the regeneration of olfactory epithelium can be stimulated by nasally administered ADSCs secreting neurotrophic factors, thereby promoting the recovery of odor aversion behavior in vivo.

Keywords: adipose-derived mesenchymal stem cells; neurotrophic factor; olfactory impairment; regenerative medicine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes
Animals
Male
Mesenchymal Stem Cells*
Mice
Mice, Inbred C57BL
Nerve Growth Factor* / metabolism
Olfactory Mucosa / metabolism

Substances

Nerve Growth Factor

Grants and funding

This study was funded in part by the KAKENHI program of the Japan Society for the Promotion of Science (JP17K11369 and JP21K09592 to H.S., JP19K18822 to T.I., JP21H03090 to T.M.), the Kanazawa Medical University Research Project “Strategic Development and Innovation in Cell Therapy” (RP2017-06, RP2020-02 to H.S.), Grant for Assist KAKEN from Kanazawa Medical University (K2021-11 to T.I.), and by a grant for collaborative research from the Kanazawa Medical University (C2020-1, C2021-2 to H.S., Y.I., and T.M.). The funding agencies had no role in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the article for publication.