Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea
Abstract Background Inner ear hair cells as mechanoreceptors are extremely important for hearing. Defects in hair cells are a major cause of deafness. Induced pluripotent stem cells (iPSCs) are promising for regenerating inner ear hair cells and treating hearing loss. Here, we investigated migration...
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BMC
2018-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0967-1 |
| _version_ | 1818560701228122112 |
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| author | Jianling Chen Fanfan Hong Cui Zhang Liang Li Cuicui Wang Haosong Shi Yong Fu Jinfu Wang |
| author_facet | Jianling Chen Fanfan Hong Cui Zhang Liang Li Cuicui Wang Haosong Shi Yong Fu Jinfu Wang |
| author_sort | Jianling Chen |
| collection | DOAJ |
| description | Abstract Background Inner ear hair cells as mechanoreceptors are extremely important for hearing. Defects in hair cells are a major cause of deafness. Induced pluripotent stem cells (iPSCs) are promising for regenerating inner ear hair cells and treating hearing loss. Here, we investigated migration, differentiation, and synaptic connections of transplanted otic epithelial progenitors (OEPs) derived from human iPSCs in mouse cochlea. Methods Human urinary cells isolated from a healthy donor were reprogramed to form iPSCs that were induced to differentiate into OEPs and hair cell-like cells. Immunocytochemistry, electrophysiological examination, and scanning electron microscopy were used to examine characteristics of induced hair cell-like cells. OEP-derived hair cell-like cells were cocultured with spiral ganglion neurons (SGNs), and the markers of synaptic connections were detected using immunocytochemistry and transmission electron microscope. In vivo, OEPs derived from iPSCs were transplanted into the cochlea of mice by injection through the round window. Migration, differentiation, and synaptic connections of transplanted cells were also examined by thin cochlear sectioning and immunohistochemistry. Results The induced hair cell-like cells displayed typical morphological characteristics and electrophysiological properties specific to inner hair cells. In vitro, OEP-derived hair cell-like cells formed synaptic connections with SGNs in coculture. In vivo, some of the transplanted cells migrated to the site of the resident hair cells in the organ of Corti, differentiated into hair cell-like cells, and formed synaptic connections with native SGNs. Conclusions We conclude that the transplantation of OEPs is feasible for the regeneration of hair cells. These results present a substantial reference for a cell-based therapy for the loss of hair cells. |
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| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-14T00:41:39Z |
| publishDate | 2018-08-01 |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-2aa5e7779e2243d29944d4067ed9de292022-12-21T23:24:20ZengBMCStem Cell Research & Therapy1757-65122018-08-019111510.1186/s13287-018-0967-1Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochleaJianling Chen0Fanfan Hong1Cui Zhang2Liang Li3Cuicui Wang4Haosong Shi5Yong Fu6Jinfu Wang7Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus of Zhejiang UniversityInstitute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus of Zhejiang UniversityInstitute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus of Zhejiang UniversityInstitute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus of Zhejiang UniversityInstitute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus of Zhejiang UniversityDepartment of Otorhinolaryngology, the Sixth People’s Hospital, School of Medicine, Shanghai Jiaotong UniversityDepartment of ENT, Head and Neck Surgery, the Children’s Hospital, Zhejiang University School of MedicineInstitute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus of Zhejiang UniversityAbstract Background Inner ear hair cells as mechanoreceptors are extremely important for hearing. Defects in hair cells are a major cause of deafness. Induced pluripotent stem cells (iPSCs) are promising for regenerating inner ear hair cells and treating hearing loss. Here, we investigated migration, differentiation, and synaptic connections of transplanted otic epithelial progenitors (OEPs) derived from human iPSCs in mouse cochlea. Methods Human urinary cells isolated from a healthy donor were reprogramed to form iPSCs that were induced to differentiate into OEPs and hair cell-like cells. Immunocytochemistry, electrophysiological examination, and scanning electron microscopy were used to examine characteristics of induced hair cell-like cells. OEP-derived hair cell-like cells were cocultured with spiral ganglion neurons (SGNs), and the markers of synaptic connections were detected using immunocytochemistry and transmission electron microscope. In vivo, OEPs derived from iPSCs were transplanted into the cochlea of mice by injection through the round window. Migration, differentiation, and synaptic connections of transplanted cells were also examined by thin cochlear sectioning and immunohistochemistry. Results The induced hair cell-like cells displayed typical morphological characteristics and electrophysiological properties specific to inner hair cells. In vitro, OEP-derived hair cell-like cells formed synaptic connections with SGNs in coculture. In vivo, some of the transplanted cells migrated to the site of the resident hair cells in the organ of Corti, differentiated into hair cell-like cells, and formed synaptic connections with native SGNs. Conclusions We conclude that the transplantation of OEPs is feasible for the regeneration of hair cells. These results present a substantial reference for a cell-based therapy for the loss of hair cells.http://link.springer.com/article/10.1186/s13287-018-0967-1Sensorineural hearing lossInduced pluripotent stem cellsHair cell-like cellsOtic epithelial progenitorsSynaptic connection |
| spellingShingle | Jianling Chen Fanfan Hong Cui Zhang Liang Li Cuicui Wang Haosong Shi Yong Fu Jinfu Wang Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea Stem Cell Research & Therapy Sensorineural hearing loss Induced pluripotent stem cells Hair cell-like cells Otic epithelial progenitors Synaptic connection |
| title | Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea |
| title_full | Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea |
| title_fullStr | Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea |
| title_full_unstemmed | Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea |
| title_short | Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea |
| title_sort | differentiation and transplantation of human induced pluripotent stem cell derived otic epithelial progenitors in mouse cochlea |
| topic | Sensorineural hearing loss Induced pluripotent stem cells Hair cell-like cells Otic epithelial progenitors Synaptic connection |
| url | http://link.springer.com/article/10.1186/s13287-018-0967-1 |
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