Mesenchymal stem cells for prevention of ototoxicity induced by cisplatin.

In the mammalian cochlea, mesenchymal stem cells lose their properties shortly after embryo development, therefore only an exogenous transplantation of stem cells could induce regeneration of tissues damaged by acoustic traumas or exposure to ototoxic agents. Several studies deal with the use of antioxidants or anti-inflammatory molecules to prevent ototoxicity induced by cisplatin (Cpt), an antineoplastic agent commonly employed in clinical treatments of solid tumors, but a complete protection from hearing loss caused by Cpt has never been reported. Our study concerns the use of mesenchymal stem cells to prevent ototoxicity caused by exposure to Cpt. Human mesenchymal stem cells (HMSC) were isolated from adipose tissues from healthy donors undergoing plastic surgery and injected in a rat animal model. Anaesthetized rats were pretreated with an intratympanic (IT) bilateral injection of HMSC and with an intraperitoneal injection (IP) of Cpt (4.6 mg/Kg) for two consecutive days, to a final cumulative dose of 14 mg/Kg. The auditory threshold was monitored before and after treatment by Auditory Brain Response. Four days after treatment all animals were painlessly sacrificed for histological analyses. The results show that the cumulative Cpt dose caused a significant hearing loss with cochlear damage, including loss of hair cells in the basal region. In controls treated only with normal saline an inflammatory response, but not hypoacousia, was observed near the round window, and the same effect was observed in controls treated only with HMSC. The IT pretreatment with HMSC before exposure to Cpt significantly reduced hearing loss caused by Cpt, as confirmed by a lower histological damage of hair cells. These data show for the first time that stem cells may be used to prevent Cpt-induced damage. Further studies are required on the biochemical and molecular mechanisms of action/protection exerted by these cells against ototoxic damage.