ИСТИНА

Couple infertility is a severe medical problem worldwide, and the impact of male factor becomes substantial or even prevailing in some regions. In general, male infertility emanates from primary spermatogenic failure caused by conditions other than obstruction of male genital tract or hypothalamic-pituitary malfunction. Different components of spermatogonial stem cell (SSC) niche can be involved in the development of male infertility. The niche itself is supported by complex intercellular interactions including a plethora of paracrine signals. So far there is a lack of effective therapy for the majority of male infertility cases. Thus, the research and development of novel therapies to recover spermatogenesis is actual. Multipotent mesenchymal stem/stromal cells (MSC) conditioned medium (CM) could be a promising therapeutic tool as MSC secrete a wide spectrum of paracrine factors supporting proliferation, survival and differentiation of cells in different resident stem cell niches. Importantly, according to our previous studies MSC secrete molecules supporting functions and viability of SSC, Leydig and Sertoli cells. We developed the combined drug based on human MSC CM products and collagen as a protective depo for MSC secreted components. Rat abdominal cryptorchidism model of spermatogenesis failure was used. We determined that either combined biomaterial containing MSC CM or MSC cell therapy recovered injured SSC niche. Importantly, the total and moving spermatozoa fractions reflecting the reproductive potential had increased after the therapy. Using histologic and immunohistochemical analyses we assessed the involvement of several regenerative mechanisms such as increase of Sertoli and Leydig cells number, proliferation of SSC and angiogenesis in recovery process at different time points after the injury (1 and 3 months). By analyzing serum concentrations of androgens we revealed the indirect connection between Leydig cells’ function and SSC niche recovery. According to our results the application of combined biomaterial based on human MSC CM and collagen gel can be promising, and it could be more preferable to cell therapy with MSC. Funding Source: Study was supported by RSF (#14- 15-00439) and conducted using biomaterial collected under RSF grant #14-50-00029 and equipment purchased as a part of Moscow State University Program of Development.