Fig. 5. Localization and in vivo differentiation of transplanted human mesenchymal stem cells (hMSCs). (A-D) Immunohistochemical study was performed eight weeks after neural-induced hMSCs (NI-hMSCs) transplantation into 10% neomycin-treated guinea pig inner ear. (A) Transplanted hMSCs stained with human nuclei (hNuclei; red) were found along the cochlear nerve fibers close to the organ of Corti. (B) Human nuclei expressing transplant derived-hMSCs (red) were located in the inner hair cell layer (arrow) and supporting cell layer (arrowhead). (C) NI-hMSCs (green) migrated into the damaged spiral ganglion were stained with microtubule-associated protein (MAP2) (red), and merged as yellow. These results depict that NI-hMSCs have the capacity not only to survive and localize in the inner ear, but also to regenerate or replace the damaged cochlear cell types. (D) Quantification of spiral ganglion neuron (MAP2⁺) and transplant-derived cell (hNuclei⁺) counts indicated that transplanted hMSCs were transdifferentiated into mature neurons in the spiral ganglion. CN, cochlear nerve fibers; OC, organ of Corti; SG, spiral ganglion; SL, spiral limbus; SM, scala media; ST, scala tympani; SV, scala vestibule.