Evaluation of the Effect of Mesenchymal Stem Cells on Cisplatin Induced Toxicity in Neuroblastoma Tumor Model

Objective: High-dose cisplatin (CDDP) causes dose-limiting side effects in neuroblastoma (NB) treatment. Mesenchymal stem cells (MSC) are a current research area. The aim of this study is to assess the interaction of MSC with CDDP in nude mouse NB model. Methods: Athymic male nude mice (n=28) thatbhad basal auditory tests, with subcutaneous NB were randomized to control, CDDP, MSC and CDDP+MSC treatment groups. Seven days later, hearing tests were repeatedand the animals were sacrificed. Necrosis, apoptosis and viabilitywere assessed in tumors. MSC rate within the tumor was assessed with flow cytometry for triple CD34+ CD44+ and CD117- expression. Expression of the cochlear cell proteins of calretinin, math-1 and myosin2A were immunohistochemically assessed. Results: Tumor tissues were found to have statistically significantly higher levels of necrosis in CDDP and CDDP+MSC groups. MSC did not change the tumor dimensions in the CDDP group. MSC group had higher triple CD34+ CD44+ and CD117- expression within tumor tissue compared to the control and CDDP groups. In the inner ear, the expression of cochlear cell proteins calretinin, math-1 and myosin2A were identified to be highest in MSC group. 15-decibel loss at 12, 16, 20 and 32 kHz frequencies with CDDP was resolved with MSC administration. Conclusion: MSC prevented hearing loss caused by CDDP without disrupting the antitumor effect of CDDP. Systemic MSC may be assessed for clinical use to reduce the side effects of CDDP.