Induction of Spermatogenesis by Bone Marrow-derived Mesenchymal Stem Cells in Busulfan-induced Azoospermia in Hamste

Abstract

BackgroundBone marrow-derived mesenchymal stem cells (BM-MSCs) have potential of differentiation and they secrete anti-inflammatory cytokines and growth factors which make them appropriate for cell therapy.Aim of the WorkWere to evaluate the healing effect of BM-MSCs transplantation on germinal cells of busulfan-induced azoospermic hamsters.Material and MethodsIn the present experimental case control study, BM-MSCs were isolated from bone marrow of donor albino hamsters. Five mature male recipient hamsters received two doses of 10 mg/kg of busulfan with 21 days interval to stop endogenous spermatogenesis. After induction of azoospermia, right testis of hamsters was injected with 106 BM-MSCs via efferent duct and the left one remained as azoospermia control testis. Five normal mature hamsters were selected as normal intact control. After 35 days, testes and epididymis of three groups were removed for histological evaluation.ResultsHistomorphological analyses of BM-MSCs treated testes and epididymis showed the epithelial tissue of seminiferous tubules had normal morphology and spermatozoa were present in epididymis tubes. Spermatogenesis was observed in most cell-treated seminiferous tubules. The untreated seminiferous tubules were empty.ConclusionTransplanted BM-MSCs could successfully induce spermatogenesis in seminiferous tubules of azoospermic hamster. Therefore, BM-MSCs can be an attractive candidate in cell transplantation of azoospermia.

Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells into the Testes of Infertile Male Rats and New Germ Cell Formation

“…However others reported that transplanted MSCs not only had the potency for differentiation into GCs (28), but also they could fully differentiate into sperm and regenerate spermatogenesis (27, 29). A recent study has showed the supportive role of BM-MSCs for recovery of spermatogenesis after transplantation into the testes of busulfan-induced infertile male hamsters (30). In the current study, we evaluated the fate of rat autologous BM-MSCs after transplantation into the testes of busulfan-induced infertile rats at 4, 6 and 8 weeks after transplantation.…”

“…Some in vitro studies on MSCs from different species have shown that under appropriate conditions and with proper inducers, MSCs had the capability to differentiate into male GCs (13, 18–24). Although a number of researchers believe that MSCs do not impact regeneration of testicular gametogenesis in infertile animal models (25, 26), other studies have shown that MSCs positively affect reconstruction of germinal epithelium and restoration of fertility (27–30). …”

Hyperthermia versus busulfan: Finding the effective method in animal model of azoospermia induction

“…According to the literature, many studies have used the animal model of azoospermia for evaluating stem cell transplantation efficacy (Abuelhija et al, ; Azizollahi et al, ; Forand, Messiaen, Habert, & Bernardino‐Sgherri, ; Karimaghai et al, ; Koruji, Movahedin, Mowla, Gourabi, & Jabbary Arfaee, ; Lysiak, Turner, & Turner, ; Makoolati, Movahedin, Forouzandeh‐Moghadam, Naghdi, & Koruji, ; Rahmanifar et al, ; Tamadon et al, ; Vahdati, Fathi, Hajihoseini, Aliborzi, & Hosseini, ). The best model for this purpose should be depleting completely from all spermatogenic cells, especially spermatogonia because of the ability of division.…”

Can mesenchymal stem cells improve spermatogonial stem cell transplantation efficiency?

“…Although donor MSCs failed to complete meiosis, above studies emphasized the role of prior induction of MSCs with RA. Mesenchymal stem cell transplantation (MSCT) has resulted in an improved spermatogenesis index in the rat (Mehrabani et al ., and Rahmanifar et al ., ) and hamster (Tamadon et al ., ). Moreover, MSCs from higher order species also showed trans‐differentiation to pre‐meiotic ( STRA8 ) and post‐meiotic ( PRM1 ) germ cells after RA treatment for 14 days in culture (Wang et al ., ).…”