Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea

• Published in: Stem cell research & therapy 2018-08, Vol.9 (1), p.230-230, Article 230
• Main Authors: Chen, Jianling, Hong, Fanfan, Zhang, Cui, Li, Liang, Wang, Cuicui, Shi, Haosong, Fu, Yong, Wang, Jinfu
• Format: Article
• Language: English
• Subjects: Adult; Animals; Biomarkers - metabolism; Care and treatment; Cell Differentiation; Cell migration; Cell Movement; Cochlea; Cochlea - metabolism; Cochlea - pathology; Coculture Techniques; Deafness; Epithelial Cells - cytology; Epithelial Cells - metabolism; Female; Gene Expression Regulation; Hair cell-like cells; Hair cells; Hair Cells, Auditory, Inner - metabolism; Hair Cells, Auditory, Inner - pathology; Hearing loss; Hearing protection; Humans; Immunocytochemistry; Immunohistochemistry; Induced pluripotent stem cells; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Induced Pluripotent Stem Cells - transplantation; Inhibitory postsynaptic potentials; Inner ear; Mammals; Mechanoreceptors; Mice; Mice, Knockout; Mice, Nude; Morphology; Neurons; Neurons - metabolism; Neurons - ultrastructure; Organ of Corti; Otic epithelial progenitors; Penicillin; Physical characteristics; Pluripotency; Regeneration; Regeneration - genetics; Scanning electron microscopy; Sectioning; Sensorineural hearing loss; Spiral ganglion; Stem Cell Transplantation; Stem cells; Sulfate Transporters - deficiency; Sulfate Transporters - genetics; Synapses; Synapses - metabolism; Synapses - ultrastructure; Synaptic connection; Transcription Factors - genetics; Transcription Factors - metabolism; Transmission electron microscopes; Transplantation, Heterologous; Transplants & implants; Urine
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-018-0967-1

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. 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. 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. 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.