Sensory cell regeneration and stem cells: what we have already achieved in the management of deafness.
OBJECTIVE
Genetic manipulation of the cell-cycle exit, induction of new hair cells (HCs) through gene modification therapy, and introduction of stem cells (SCs) into damaged cochleas potentially offer exciting new strategies in treating sensorineural hearing loss.


METHODS
Literature review from Medline and database sources.


METHODS
Ex vivo models, animal studies, in vitro studies, and review articles.


RESULTS
Embryonic SCs, neural SCs, or bone marrow SCs survive in the mammalian inner ear after transplantation. The scala media and the modiolus seem more functionally appropriate injection sites. The clear evidence that transplanted neural SCs can adopt the morphologic phenotypes of HCs was the most significant milestone achieved in the related research. The normal cytoarchitecture in the organ of Corti may also be restored through mouse atonal homologue 1 transgene expression and transduction of the nonsensory cells, producing clinically measured improvement in hearing thresholds. Embryonic SC-derived neurons have the potential for synapse formation with auditory HCs and reinnervation of the auditory epithelia. However, fluctuations in survival rates, functional recovery of the spiral-ganglion neurons, integration to the host tissue, and potential immune barriers are also areas of utmost importance.


CONCLUSIONS
There is an already exciting progress in the fields of sensory cell regeneration and SC research in an attempt to restore hearing or prevent deafness. However, further understanding of the underlying mechanisms of auditory genetics, continuing investigation of the human genome, refinement of the delivering techniques, and specification of the therapeutic strategies have to be developed before functional regeneration of the cochlea can be achieved in clinical practice.
Vlastarakos
Petros V
PV
ENT Department, Hippokrateion General Hospital of Athens, Athens, Greece. pevlast@hotmail.com
Nikolopoulos
Thomas P
TP
Tavoulari
Evangelia
E
Papacharalambous
George
G
Tzagaroulakis
Antonios
A
Dazert
Stefan
S
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D003051:Cochlea / Q000473:pathology; D003053:Cochlear Duct / Q000473:pathology; D003638:Deafness / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D006198:Hair Cells, Auditory / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D009925:Organ of Corti / Q000473:pathology; D010641:Phenotype; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*