Journal
STEM CELL RESEARCH & THERAPY
Volume 12, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13287-021-02403-9
Keywords
ES cell; Cell transplantation; Selective ablation; Regeneration; Cochlea
Funding
- National Institutes of Health/National Institutes on Deafness and Other Communicative Disorders [R01 DC01391201]
- Med-El Corporation
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The study demonstrates the feasibility of human stem cell engraftment into an ablated mouse organ of Corti, showing increased engraftment and differentiation of transplanted cells into hair and supporting cell immunophenotypes after hair cell ablation prior to transplantation.
BackgroundHearing loss affects 25% of the population at ages 60-69years. Loss of the hair cells of the inner ear commonly underlies deafness and once lost this cell type cannot spontaneously regenerate in higher vertebrates. As a result, there is a need for the development of regenerative strategies to replace hair cells once lost. Stem cell-based therapies are one such strategy and offer promise for cell replacement in a variety of tissues. A number of investigators have previously demonstrated successful implantation, and certain level of regeneration of hair and supporting cells in both avian and mammalian models using rodent pluripotent stem cells. However, the ability of human stem cells to engraft and generate differentiated cell types in the inner ear is not well understood.MethodsWe differentiate human pluripotent stem cells to the pre-placodal stage in vitro then transplant them into the mouse cochlea after selective and complete lesioning of the endogenous population of hair cells.ResultsWe demonstrate that hair cell ablation prior to transplantation leads to increased engraftment in the auditory sensory epithelium, the organ of Corti, as well as differentiation of transplanted cells into hair and supporting cell immunophenotypes.ConclusionWe have demonstrated the feasibility of human stem cell engraftment into an ablated mouse organ of Corti.
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