Beneficial effects of adipose-derived stromal vascular fraction on testicular injury caused by busulfan

Abstract

Introduction and Objectives: Busulfan, a commonly used chemotherapeutic agent, attaches to one of the DNA strands of the cancer cells thus prevents them from dividing. Male infertility is one of the side effects of cancer treatment. Preserving or restoring fertility of these patients constitute an important research area. In recent years, various studies have been published investigating the therapeutic effects of stem cell applications in various diseases. Adipose tissue-derived stromal vascular fraction (SVF), obtained by enzymatic and/or mechanical disintegration of adipose tissue, contains endothelial progenitor cells, hematopoietic cells, pericytes, macrophages, fibroblasts and various growth factors in addition to the stem cells. This study aimed to investigate the therapeutic effects of SVF on busulfan-induced testicular damage. Materials and Methods: Twenty-four male rats were randomly divided into control, busulfan, SVF and busulfan+SVF group. Testicular damage was induced by single intraperitoneal busulfan (35 mg/kg) application. SVF obtained from human adipose tissue using Lipocube SVFTM was injected into the testicles of rats 5 weeks after busulfan application. Histopathological, biochemical and western blotting analyses were performed on sperm and testicular samples. Results: Vacuolization, tubular degeneration and atrophy were evident in busulfan group. The mean damage score (OHS) of this group was higher than control (p<0.001) and busulfan + SVF (p=0.006) group. The mean serum total oxidant level (TOS) was higher than control (p<0.05) and busulfan+SVF (p<0.005) group. Mean serum and tissue total antioxidant levels (TAS) were lower than those in the control (p≤0.001; p<0.005) and busulfan+SVF (p<0.005) group. The mean TUNEL + cell count and tissue Bax-Bcl-2 level of busulfan group were higher than control (p<0.001, p<0.05) group. The mean tissue CD-90 level in busulfan group was higher than control (p<0.05) and busulfan+SVF (p<0.001) group. Tissue ATG5 level of this group was also higher than control (p<0.05) and busulfan+SVF (p<0.05) group. Similarly, the mean NF-kB level was higher than control (p<0.05) and busulfan+SVF (p<0.001) group. On the contrary, the mean tissue TGF-β1 level was lower than the busulfan+SVF (p<0.001) group. The mean healthy sperm count in busulfan group was also lower than control (p<0.001) and busulfan+SVF (p<0.001) groups. Conclusion: It was concluded that SVF injection reduced busulfan-induced oxidative stress and tissue damage and increased sperm count. SVF may be a promising and effective therapeutic agent in the elimination of testicular damage caused by busulfan toxicity.