Enhanced survival of bone-marrow-derived pluripotent stem cells in an animal model of auditory neuropathy.
OBJECTIVE
The loss of spiral ganglion neurons (SGNs) is one of the major causes of profound sensorineural hearing loss (SNHL). Stem cell replacement therapy, which is still in its infancy, has the potential to treat or cure those who suffer from an array of illnesses and degenerative neurologic disorders, including sensorineural deafness (SNHL). Little is known about the potentials of mesenchymal stem cells (MSCs) and their ability to take on properties of SGNs. The two main purposes of this study were to evaluate the survival of mouse MSCs transplanted into normal and ouabain-treated gerbil cochleae and to determine the migratory patterns of MSCs with two differing injection methods.


METHODS
Thirty-two Mongolian gerbils, 3 to 4 months old, were used as recipients, and four 6-week-old TgN(ACTbEGFP) mice that ubiquitously express green fluorescent protein (GFP) were used as donors.


METHODS
The animals were deafened by ouabain, which damaged SGNs while leaving hair cell systems intact. After 4 weeks of recovery, the animals received an intraperilymphatic transplantation of 1.0x10(6) GFP-positive undifferentiated MSCs via two different injection methods: scala tympani injection and modiolar injection. Seven days after the transplantation, the survival of MSCs was evaluated by microscopic examination of frozen sections cut through the cochleae of the recipient animals. The number of profiles was counted on the five most central modiolar sections. One-way analyses of variance (ANOVA) were used to determine any significantdifferences among mean profile counts across the experimental conditions.


RESULTS
Our findings indicated that undifferentiated MSCs were able to survive in the modiolus both in the control and the ouabain-treated cochleae. The average number of profiles found in the modiolus was greater in the ouabain-treated cochleae than in the control cochleae. This difference was statistically significant (P<.01) as determined using a one-way ANOVA and an ad hoc Tukey-Kramer's test. With the scala tympani injection, there were no profiles found in the modiolus either in the control or ouabain-treated cochleae. This finding may indicate that donor MSCs need to be directly injected into the modiolus to replace injured SGNs. Finally, there was no evidence of hyperacute rejection in any of the gerbils despite the use of xenotransplantation.


CONCLUSIONS
These findings may have important clinical implications as a means of delivering MSCs in the cochlea for stem-cell replacement therapy. Survival of transplanted MSCs into the modiolus of the cochlea may result in regeneration of damaged SGNs.
Matsuoka
Akihiro J
AJ
Department of Otolaryngology-Head and Neck Surgery, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. amatsuok@iupui.edu
Kondo
Takako
T
Miyamoto
Richard T
RT
Hashino
Eri
E
D000818:Animals; D002470:Cell Survival; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D003056:Cochlear Nerve / Q000473:pathology* / Q000601:surgery*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005163:Factor Analysis, Statistical; D005260:Female; D005849:Gerbillinae; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000473:pathology* / Q000601:surgery*; D007267:Injections; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D018613:Microscopy, Confocal; D010042:Ouabain; D010523:Peripheral Nervous System Diseases / Q000473:pathology* / Q000601:surgery*; D039904:Pluripotent Stem Cells / Q000637:transplantation*; D013136:Spiral Ganglion / Q000473:pathology*; D014183:Transplantation, Heterologous; D014432:Tympanic Membrane
D004791:Enzyme Inhibitors; D010042:Ouabain