Inner ear progenitor cells can be generated in vitro from human bone marrow mesenchymal stem cells

Abstract

Aim: Mouse mesenchymal stem cells (MSCs) can generate sensory neurons and produce inner ear hair cell-like cells. An equivalent source from humans is highly desirable, given their potential application in patient-specific regenerative therapies for deafness. In this study, we explored the ability of human MSCs (hMSCs) to differentiate into otic lineages. Materials & methods: hMSCs were exposed to culture media conditioned by human fetal auditory stem cells. Results: Conditioned media induced the expression of otic progenitor markers PAX8, PAX2, GATA3 and SOX2. After 4 weeks, cells coexpressed ATOH1, MYO7A and POU4F3 (indicators of hair cell lineage) or neuronal markers NEUROG1, POU4F1 and NEFH. Inhibition of WNT signaling prevented differentiation into otic progenitors, while WNT activation partially phenocopied results seen with the conditioned media. Conclusion: This study demonstrates that hMSCs can be driven to express key genes found in the otic lineages and thereby promotes their status as candidates for regenerative therapies for deafness.