Can mesenchymal stem cells improve spermatogonial stem cell transplantation efficiency?

Abstract

SUMMARYImproved treatments have led to an increased survival rate in cancer patients. However, in pre-pubertal boys, these gonadotoxic treatments can result in the depletion of the spermatogonial stem cell (SSC) pool causing lifelong infertility. SSC transplantation has been proposed as a promising technique to preserve the fertility of these patients. In mice, this technique has resulted in live-born offspring, but the efficiency of colonization remained low. This could be because of a deficient microenvironment, leading to apoptosis of the transplanted SSCs. Interestingly, mesenchymal stem cells (MSCs), being multipotent and easy to isolate and multiply in vitro, are nowadays successfully and widely used in regenerative medicine. Here, we shortly review the current understanding of MSC and SSC biology, and we hypothesize that a combined MSC-SSC transplantation might improve the efficiency of SSC colonization and differentiation as paracrine factors from MSCs may contribute to the SSC niche.

The antineoplastic busulphan impairs peritubular and Leydig cells, and vitamin B12 stimulates spermatogonia proliferation and prevents busulphan-induced germ cell death

“…Studies have emphasized on the important role of oncologists regarding the reproductive and fertility status of their patients, including the hormonal health [1]. In pediatric patients submitted to therapy with busulphan (Bu), an alkylating agent used for bone marrow transplantation [2], the recovery of spermatogenesis has been a slow progressive process [3]. After treatment with Bu plus cyclophosphamide or Bu alone, a few patients showed recovery of hormonal levels and/or sperm production after an average of 2 to 5 years post-transplant [4][5][6].…”

<p>Role of stem cells in fertility preservation: current insights</p>

“…139 Moreover, pure MSCs (CD45 -Sca1 + Lin -) isolated from bone marrow of GFP + mice injected into testes of busulfan-treated GFPmice resulted in more STs presenting spermatogenesis (70%) compared to injection of hematopoietic SCs (CD45 + Sca1 + Lin -) (18%) or DMEM (19%). 15 Pretreatment of MSCs before transplantation was also evaluated with the objective of improving SSC-transplantation efficiency. Interestingly, while cotransplantation of SSCs with or without TGFβ1-treated MSCs in sterilized mice testes resulted in an equivalent resumption of endogenous spermatogenesis, a higher proportion of STs containing donor-derived spermatogenesis was observed when TGFβ1-treated MSCs were cotransplanted with SSCs.…”

“…Restoration of the damaged SSC niche with mesenchymal stem cells (MSCs) was also recently proposed to enhance or restore endogenous spermatogenesis. 15 For women, cryopreservation of oocytes or embryos is the most common way to preserve fertility. 16,17 However, while oocyte cryopreservation may also be proposed to adolescent girls, it cannot be proposed before puberty or to adult women requiring urgent therapy.…”

Roles for Kisspeptin in proliferation and differentiation of spermatogonial cells isolated from mice offspring when the cells are cocultured with somatic cells

“…TP 1 and TP 2 have also important roles for generation of fertile sperms. 15 Sertoli cells are the only type of somatic cells interacting directly with germ cells, and due to this, they take a major role in regulation of selfrenewal, 16 proliferation, and survival 17 in SCs. 3 Somatic cells (Sertoli and Leydig) have cross-talks with SCs in their niche.…”

“…20 The ability of Leydig cells for the production of testosterone is by far higher in adult than in old rats. 15 Somatic cells exert their effects on SCs by releasing factors like GDNF and EGE2. 21 Differentiation of SCs also occurs in their niche.…”