Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear.
The cochlear sensory epithelium and spiral ganglion neurons (SGNs) in the adult mammalian inner ear do not regenerate following severe injury. To replace the degenerated SGNs, neural stem cell (NSC) is an attractive alternative for substitution cell therapy. In this study, adult mouse NSCs were transplanted into normal and deafened inner ears of guinea pigs. To more efficiently drive the implanted cells into a neuronal fate, NSCs were also transduced with neurogenin 2 (ngn2) before transplantation. In deafened inner ears and in animals transplanted with ngn2-transduced NSCs, surviving cells expressed the neuronal marker neural class III beta-tubulin. Transplanted cells were found close to the sensory epithelium and adjacent to the SGNs and their peripheral processes. The results illustrate that adult NSCs can survive and differentiate in the injured inner ear. It also demonstrates the feasibility of gene transfer to generate specific progeny for cell replacement therapy in the inner ear.
Hu
Zhengqing
Z
Center for Hearing and Communication Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Zhengqing.hu@cfh.ki.se
Wei
Dongguang
D
Johansson
Clas B
CB
Holmström
Niklas
N
Duan
Maoli
M
Frisén
Jonas
J
Ulfendahl
Mats
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics; D003051:Cochlea / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D018014:Gene Transfer Techniques; D006085:Graft Survival / Q000502:physiology*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D013136:Spiral Ganglion / Q000166:cytology / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D014404:Tubulin; C102938:Neurog2 protein, mouse