Histological Study of the Potential Therapeutic Effect of Bone Marrow Derived Mesenchymal Stem Cells Versus their Secreted Extracellular Vesicles on Rats’ Seminiferous Tubules Following Busulfan Induced Toxicity

Document Type : Original Article

Authors

1 assistant lecturer of histology faculty of medicine -alexandria university

2 histology& cell biology,faculty of medicine,alexandria university ,alexandria .egypt

3 Professor of Histology and Cell Biology, Faculty of Medicine, University of Alexandria.

4 histology and cell biology ,alexandria egypt

Abstract

Introduction: Busulfan, an alkylating chemotherapeutic agent commonly used to induce myeloablation in leukemic patients, unfortunately leads to azoospermia and infertility in cancer survivors. Bone marrow derived mesenchymal stem cells (BM-MSCs) and their secreted extracellular vesicles (EVs) are emerging promising treatment modalities for treating testicular injury by busulfan.
Aim of the Work: To compare the therapeutic potential of BM-MSCs and EVs in attenuating histological and biochemical changes induced by busulfan on rats’ seminiferous tubules.
Materials and Methods: Six young male albino rats were utilized for isolation of BM-MSCs and EVs. Fifty-eight adult male rats were divided into group I (control group) including 24 rats subdivided equally into 3 subgroups IA, IB&IC, group II (n=10, single I.P of 40mg/kg busulfan) 2 were sacrificed after 48 hrs for homing, group III (n=8, single injection of BM-MSCs 1x 106 cells/ 1 ml into the efferent ducts, group IV (n=8, single injection 40 μg MSC-EVs into the efferent ducts (&group V (n=8, left for recovery assessment), rats were sacrificed after 28 days. Blood and tissue samples were collected for biochemical analysis. Semen samples were obtained to measure sperm count and motile sperm percent. The testes were processed for light and electron microscopic examination and estimation of Johnsen score. Statistical analyses of the obtained data were performed.
Results: Busulfan induced disrupted architecture of seminiferous tubules with loss of spermatogenic cells with intercellular vacuolation and nearly empty lumina which was confirmed by ultrastructural findings. There was a statistically significant decrease in serum testosterone levels, antioxidant markers, sperm parameters and Johnsen score. Concurrently, there was a statistically significant increase in oxidant profiles. Treatment with BM-MSCs ameliorated histological & biochemical changes in seminiferous tubules. However, administration of EVs yielded better results.
Conclusion: EVs exhibited better therapeutic effects than BM-MSCs in alleviating busulfan induced testicular injury.

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