A.A. Kamalov - Dr.Sc. (Med), Professor, Academician RAS, Director, Medical Research and Education Center, Lo-monosov Moscow State University; Head of the Department of Urology and Andrology, Faculty of Medicine, Lomo-nosov Moscow State University E-mail: armais.kamalov@rambler.ru V.I. Kirpatovsky - Dr.Sc. (Med), Professor, Doctor, Medical Research and Education Center, Lomonosov Moscow State University; Head of the Laboratory of Experimental Modeling of Urological Diseases, Urology Scientific Re-search Institute n.a. N.A. Lopatkin  FGBU branch «Federal medical research radiology center» of the Ministry of Health of Russian Federation(Moscow) E-mail: vladkirp@yandex.ru D.A. Ohobotov - Ph.D. (Med.), Urologist, Medical Research and Education Center, Lomonosov Moscow State Uni-versity University, Senior Lecturer, Andrology and Urology Faculty of Fundamental Medicine, Lomonosov Moscow State University Lomonosov E-mail: 14072003@rambler.ru A.Yu. Efimenko - Ph.D. (Med.), Senior Research Scientist, Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University E-mail: efimenkoan@gmail.com P.I. Makarevich - Ph.D. (Med.), Senior Research Scientist, Laboratory of Gene and Cell Therapy, Institute for Re-generative Medicine, Medical Research and Education Center, Lomonosov Moscow State University E-mail: pavel.makarevich@gmail.com G.D. Sagaradze - Post-graduate Student, Faculty of Medicine, Lomonosov Moscow State University E-mail: georgysagaradze@gmail.com O.A. Makarevich - Research Scientist, «Gene and Cell Therapy» Ltd. (Moscow) E-mail: go.grigorievaolga@gmail.com P.P. Nimiritskiy - Post-graduate Student, Faculty of Medicine, Lomonosov Moscow State University E-mail: nimiritsky@gmail.com N.A. Basalova - Student, Faculty of Biology, Lomonosov Moscow State University E-mail: natalia_ba@mail.ru D.M. Kamalov - Urologist, Medical Research and Education Center, Lomonosov Moscow State University E-mail: davidffm@mail.ru E.O. Osidak - Ph.D. (Biol.), Leading Research Scientist, «IMTEK» Ltd. E-mail: egorosidak@gmail.com S.P. Domogatsky - Ph.D. (Biol.), Leading Research Scientist, Laboratory Immunochemistry, Institute for Experi-mental Cardiology, Russian Cardiology Research and Production Complex, Ministry of Health, Russian Federation E-mail: spdomo@gmail.com Z.A. Akopyan - Ph.D. (Med), Vice-director, Medical Research and Education Center, Lomonosov Moscow State University E-mail: zhanna.fbm@gmail.com V.A. Tkachuk - Dr.Sc. (Biol.), Professor, Academician RAS, Dean of Faculty of Medicine, Lomonosov Moscow State University; Director, Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University E-mail: tkachuk@fbm.msu.ru

Male infertility is a widespread problem, and there is lack of effective methods for its treatment. We have developed a novel biomaterial for the stimulation of regenerative processes based on the secreted products of human mesenchymal stem/stromal cells (MSC) isolated from adipose tissue. MSC conditioned medium (MSC CM), containing bioactive factors produced by cells, has a great regenerative potential, stimulates blood circulation recovery and innervation of the tissue after injury, contributes to the activation of endogenous repair processes due to the additional attraction of stem and progenitor cells to the damaged area. In this study, we investigated the possibility of using a combination of MSC CM and type I collagen for stimulating spermatogenesis. Work was carried out on 40 adult male rats, Wistar breed groups, age 3.5-4.0 months with standard weight characteristics. Experimental cryptorchidism (2 weeks)was used as a model of infertility. All experiments were performed in accordance with the requirements of the Helsinki agreements on human treatment of animals. The series of experiments were the following: to all animals, except the untreated group, under tunica albuginea of rat testis 0.1 ml of 2,5% collagen gel mixed with MSC CM, or concentrated MSC CM (10x), or DMEM, or MSC (250x10^3 cells) were administered. Alternatively, suspension of MSC (250x10^3 cells) in DMEM was injected. Assessment of the severity of damage to the testicles evolved after a 2-week stay in the abdominal cavity was evaluated at 1 and 3 months after their re-legation. Experimental modeling of infertility in animals leads to the persistent violations, developing within 2 weeks and expressing in spermatogenesis block, reducing the total number of Sertoli cells, infertility, hypogonadism and other phenomena, that occur on the background of pronounced local immune inflammation, accompanied by focal and diffuse lymphocytic infil-tration, limfostazis, sclerosis and atrophy of the seminiferous epithelium of the seminiferous tubules. The results of our study clearly show, that the administration of MSC suspension or MSC CM combined with a collagen gel under the testis tunica albuginea effectively stimulates the recovery of spermatogenesis in the model of experimental cryp-torchidism. The maximal effect was observed at follow-up of 3 months. These results are consistent with our previous data, demonstrating that in the context of the experimental treatment of disorders of spermatogenesis in the model bilateral abdominal cryptorchidism occurs when using MSCs expressed activation spermatogenic stage, but fertility in these animals can be estimated not earlier than 70 days from the start of observation. Use of MSC CM, containing MSC secreted products, including specific growth factors to maintain viability spermatogonial stem cells (GDNF, FGF-2, etc.), in combination with a collagen gel may be an advantage approach to stimulate spermato-genesis and can be considered to be even more preferable than the administration of the cells themselves due to the various clinical and ethical problems associated with transplantation of cellular material.

 

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