Effects of growth factors on the hair cells after ototoxic treatment of the neonatal mammalian cochlea in vitro

The aim of this study was to test the possible regenerative potential of se veral molecules and growth factors such as retinoic acid (RA), insulin, epi dermal growth factor (EGF) and transforming growth factors alpha (TGF alpha ) and beta (TGF beta) on the neonatal cochlea in vitro after neomycin intox ication. Our studies show that cochlear sensory epithelium behaves differen tly while maintained in various culture conditions, although we did not obs erve regeneration whatever the molecules or growth factors tested. The otot oxic action of neomycin in vitro produced a specific death of hair cells, e xcept in the apical region. Organ of Corti of rats 3 days after birth alway s presented two regions that responded differently to the antibiotic: a wid espread scar region extending from the basal cochlea up to the beginning of the apical turn, where most hair cells had disappeared, and a second regio n called the resistance region localized in the apex, and which was more or less developed depending on culture conditions. The length of the resistan ce region was modulated by molecules or growth factors added to the feeding solution suggesting that some of them could produce a protective action on hair cells against neomycin. Slight protection effects may be found with R A and insulin, however, the most definite protection results from the combi nation of insulin with TGF alpha as shown by the large increase in the leng th of the resistance region compared to organ of Corti treated with antibio tic alone. The tested molecules and growth factors did not promote cochlear hair cell regeneration in vitro after neomycin treatment, however some of them may offer a protective action against ototoxicity. (C) 1999 Elsevier S cience B.V. All rights reserved.