Transplantation of directly converted HDF-iNSC to the scala tympani of the cochlea increases neural structure and central auditory connection in an auditory neuropathy animal model.

@article{chang2026transplantation,
  title = {{Transplantation of directly converted HDF-iNSC to the scala tympani of the cochlea increases neural structure and central auditory connection in an auditory neuropathy animal model.}},
  author = {So-Young Chang and Jee Hyun Kang and Kwang Sung Ahn and Ji Eun Choi and Sang Min Park and Soon Young Heo and Jae Yun Jung and Min Young Lee and Hosup Shim},
  journal = {Molecular medicine (Cambridge, Mass.)},
  year = {2026},
  month = aug,
  doi = {10.1186/s10020-026-01591-5},
  url = {https://europepmc.org/article/MED/42958474},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Transplantation of directly converted HDF-iNSC to the scala tympani of the cochlea increases neural structure and central auditory connection in an auditory neuropathy animal model.
AU  - So-Young Chang
AU  - Jee Hyun Kang
AU  - Kwang Sung Ahn
AU  - Ji Eun Choi
AU  - Sang Min Park
AU  - Soon Young Heo
AU  - Jae Yun Jung
AU  - Min Young Lee
AU  - Hosup Shim
PY  - 2026
DA  - 2026/08/03
JO  - Molecular medicine (Cambridge, Mass.)
DO  - 10.1186/s10020-026-01591-5
UR  - https://europepmc.org/article/MED/42958474
AB  - Background  Cochlear implants (CIs) provide effective rehabilitation for severe-to-profound hearing loss, yet their success is limited by secondary degeneration of auditory neurons. Direct transdifferentiation, which enables lineage conversion of somatic cells into neural stem cells without a pluripotent stage, offers advantages over induced pluripotent stem cells by reducing tumorigenic risk, shortening reprogramming time, and producing expandable, patient-specific cells for autologous therapy. Oct4 is a critical factor for establishing pluripotency, but it is not required for direct reprogramming. Inclusion of Oct4 can enhance reprogramming efficiency and induce a more 'plastic' cellular state, which may facilitate improved integration and functional adaptation following transplantation into the target organ.Methods  Induced neural stem cells (iNSCs) were generated from human dermal fibroblasts. We generated iNSCs by transducing the exogenous Oct4 protein in combination with Sox2, Klf4, and c-Myc. The properties of these iNSCs were characterized, and their therapeutic potential was evaluated following transplantation in an animal model of auditory neuropathy. Histologic and functional assessment were performed.Results  Immunostaining and flow cytometry results showed that human iNSCs express Nestin, Sox2, and Pax6. Constitutive expression of SKM and transient Oct4 priming induced iNSCs from HDFs under NSC-permissive culture conditions. Isolated iNSCs had similar morphological features and expression markers as control human NSCs. Transplanted human iNSCs improved cochlear cellular integrity, particularly by enhancing neural structures including neurons and nerve fibers. Although peripheral synaptic connections were not restored, synaptic marker toward the central auditory pathway was significantly increased. eABR responses showed statistically higher response in iNSC transplanted animals.Conclusion  Direct transdifferentiation provides an efficient strategy to generate autologous iNSCs capable of preserving and repairing auditory neural structures. By improving neural health, this approach has the potential to enhance CI performance, expand candidacy to patients with long-term hearing loss, and establish a novel regenerative avenue for functional hearing restoration.
SN  - 1076-1551
SN  - 1528-3658
ER  -