Transplantation of a human induced pluripotent stem cell-derived airway epithelial cell sheet into the middle ear of rats
| Autor: | Takeshi Tada, Hiroe Ohnishi, Norio Yamamoto, Fumihiko Kuwata, Yasuyuki Hayashi, Hideaki Okuyama, Tsunetaro Morino, Yoshiyuki Kasai, Hiromi Kojima, Koichi Omori |
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| Rok vydání: | 2022 |
| Předmět: |
Medicine (General)
ET Eustachian tube CPM carboxypeptidase M Middle ear PBS phosphate-buffered saline Biomedical Engineering KRT5 cytokeratin5 NBRP National BioResource Project Ac-TUB acetylated α-tubulin Biomaterials R5-920 X-SCID x-linked severe combined immunodeficient hiPSC human induced pluripotent stem cell OCT optimal cutting temperature PET polyethylene terephthalate Cholesteatoma AEC airway epithelial cell Otitis media Transplantation QH573-671 EDTA ethylenediaminetetraacetic acid HNA human nuclear antigen Induced pluripotent stem cell respiratory system MUC5AC mucin5AC Original Article PFA paraformaldehyde Cytology DAPI 4′ 6-diamidino-2-phenylindole Developmental Biology |
| Zdroj: | Regenerative Therapy Regenerative Therapy, Vol 19, Iss, Pp 77-87 (2022) |
| ISSN: | 2352-3204 |
| DOI: | 10.1016/j.reth.2022.01.001 |
| Popis: | Introduction Early postoperative regeneration of the middle ear mucosa is essential for the prevention of postoperative refractory otitis media and recurrent cholesteatoma. As a means for intractable otitis media management, we focused on human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (AECs), which have been used in upper airway mucosal regeneration and transplantation therapy. In this study, we transplanted hiPSC-derived AECs into the middle ear of immunodeficient rats. Methods Following the preparation of AEC sheets from hiPSCs, the bilateral middle ear mucosa of X-linked severe combined immunodeficient rats was scraped, and the AEC sheets were transplanted in the ears unilaterally. Results Human nuclear antigen (HNA)-positive ciliated cells were observed on the transplanted side of the middle ear cavity surface in three of six rats in the 1-week postoperative group and in three of eight rats in the 2-week postoperative group. No HNA-positive cells were found on the control side. The percentage of HNA-positive ciliated cells in the transplanted areas increased in the 2-week postoperative group compared with the 1-week group, suggesting survival of hiPSC-derived AECs. Additionally, HNA-positive ciliated cells were mainly located at sites where the original ciliated cells were localized. Immunohistochemical analysis showed that the transplanted AECs contained cytokeratin 5- and mucin 5AC-positive cells, indicating that both basal cells and goblet cells had regenerated within the middle ear cavity. Conclusions The results of this study are an important first step in the establishment of a novel transplantation therapy for chronic otitis media. Highlights • hiPSC-derived airway epithelial cells were transplanted into the middle ear of rats. • Engrafted cells mainly survived in the ciliated region of the middle ear. • Ciliated, goblet, and basal cells were confirmed in the engrafted cells. |
| Databáze: | OpenAIRE |
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