Protective effect of bone marrow-derived mesenchymal stem cells on methotrexate?induced brain and liver injury in female albino rats: Histological study

摘要

Background and Objectives : Methotrexate (MTX) is an anti-folate drug that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of MTX is often limited by its severe side effects and toxic sequelae. Bone marrow derived mesenchymal stem cells (BM-MSCs) are a novel source for cell-based therapy and regenerative medicine . Aim of the work: to investigate the possible therapeutic effect of BM-MSCs therapy on MTX induced damage in brain and liver of female albino rats. Materials and Methods: Ten Wister male albino rats of average 100 gm were served as donors for stem cells obtained from their bone marrow for isolation of BM-MSCs. Forty Wister female adult albino rats of 200-250 gm were randomly and equally divided into four groups (10 animals each). Group I ( Control group): Female rats were injected with phosphate buffer saline (PBS) and used to collect control brain & liver samples . Group II (MTX group): Female rats were injected intraperitoneally with MTX (0.5 mg /kg twice a week) for four weeks. Group III (MSCs group): Female rats were injected intraperitoneally with MTX as in group II for four weeks then received single intraperitoneal injection of 2×10⁶ BM-MSCs suspended in PBS per rat and scarified after another four weeks. Group IV (Recovery group): Female rats were injected intraperitoneally with MTX as in group II for four weeks then allowed to survive for another successive four weeks without treatment then sacrificed. Results: Histological examination of the brain sections of MTX treated groups (groups II & IV) revealed shrunken deeply stained pyramidal cells of the frontal cortex with significant increase in the number of GFAP positive immuno-reactive astrocytes and caspase-3 immuno-reactive pyramidal cells in the frontal cortex as compared to that of the control group. Liver sections of MTX treated groups (groups II & IV) showed distorted hepatic architecture as most of the hepatocytes revealed vacuolated cytoplasm. Mallory trichrome stained sections of these groups showed significant increase of collagen fibers deposition comparable to that of the control group. Nevertheless, transplantation of BM-MSCs in group III led to marked improvement of the frontal cortex. Moreover , few GFAP positive immuno-reactive astrocytes and caspase-3 positive immuno-reactive pyramidal cells were detected in the frontal cortex of rats in the same group. Remarkable improvement was recorded in the liver sections of the same group as the normal hepatic architecture was restored. In addition few collagen fibers were observed in Mallory trichrome stained sections. Conclusion: BM-MSCs administration in MTX treated rats has enormous outcome in both brain and liver.