Investigation of the Efficacy of Stem Cell Therapy in a Rat Model of Cyclophosphamide-Induced Neurotoxicity.

ObjectiveCyclophosphamide (CYP) is one of the chemotherapeutic agents known to cause neurotoxicity. The aim of this study was to experimentally investigate the potential therapeutic effect of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in the prevention of CYP-related neurotoxicity.MethodsA total of 18 rats were divided into three groups: Group 1: CYP, Group 2: CYP + stem cell, Group 3: control. Groups 1 and 2 received intraperitoneal (IP) CYP for 14 days, while the control group received IP saline. Subsequently, hUC-MSCs were administered to Group 2 as treatment. Mesenchymal stem cell (MSC) treatment was initiated only after completion of cyclophosphamide (CYP) administration to induce neurotoxicit. At the end of the first month, the animals were euthanized. Brain tissues were collected and examined using H&E, neurofilament immunostaining, and silver nitrate staining. Neurodegeneration and regeneration in the cerebral and cerebellar cortices were evaluated in a blinded histopathological manner. Histopathological evaluation of degeneration in the cerebral and cerebellar cortex, as well as cerebral gliosis, was performed and graded between 1 and 4 (0-25%: grade 1, 25-50%: grade 2, 50-75%: grade 3, 75-100%: grade 4).ResultsIn the CYP group (Group 1), degeneration in the cerebral and cerebellar cortex and a higher number of cerebral glial cells were significantly higher compared to the other groups (p < 0.001; p < 0.001; p < 0.001). In Group 2 (CYP + stem cell), evidence of regeneration was observed in the cerebral and cerebellar cortex, along with a reduction in cerebral glial cells (p < 0.001). The results of the stem cell-treated group were closer to those of the control group.ConclusionhUC-MSCs demonstrated a neuroprotective effect against CYP-induced neurotoxicity. Stem cell therapy may represent a promising approach to prevent the neurodegenerative effects of cytotoxic agents.