Therapeutic effect of adipose-derived mesenchymal stem cells on Cisplatin induced testicular damage in adult male albino rat.

Abstract

Infertility represents a major medical, economic, and psychological problem. Stem cells therapy for infertility has a great interest nowadays especially for cancer survivors at pre-reproductive and reproductive age.  Thirty-two adult male albino rats were used, divided equally into four groups; Group I (Control group) received isotonic saline intraperitoneally (i.p.) as vehicle. Group II (Cisplatin-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then were sacrificed after 5 days. Group III (Stem-cell-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, then after 5 days received adipose-derived mesenchymal stem cells (ADMSCs) (1 × 106). Cells were injected in the rete testis, then after 60 days, the animals were sacrificed. Group IV (Auto healing group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then left for 65 days then the animals were sacrificed. Cisplatin administration resulted in degenerative changes in the testicular architecture in the form of thickened irregular BM of seminiferous tubules. The germinal epithelium showed disorganization and marked reduction in the thickness, associated with Sertoli cells preservation. Features of apoptosis assured by elevated caspase-3 expression were noticed. The interstitium showed cellular infiltration and distorted Leydig cells. Injection of (ADMSCs) resulted in great improvement of testicular architecture and increase in the testosterone level associated with strong immune reaction of the CD-44. ADMSCs are recommended as a new treatment modality for male infertility. Abbreviation: i.p.: intraperitoneally; BM: basement membrane; ADMSCs: adipose-derived mesenchymal stem cells; WHO: World Health Organization; MSCs: mesenchymal stem cells; DMEM: Dulbecco modified eagles media; PBS: phosphate-buffered saline; FACS: fluorescence-activated cell sorting; ELISA: enzyme-linked immunosorbent assay; CP: Cisplatin; ROS: reactive oxygen species; CAT: catalase; SOD: superoxide dismutase; OS: oxidative stress; SSCs: spermatogonia stem cells; GCs: germ cells; UCMSCs: umblical cord mesenchymal stem cells; TGFb1: transforming growth factor beta-1; BMP4: Bone morphogenic protein 4; BMP8b: bone morphogenic protein 8b.