Cellular Therapy via Spermatogonial Stem Cells for Treating Impaired Spermatogenesis, Non-Obstructive Azoospermia

Abstract

Male infertility is a major health problem affecting about 8–12% of couples worldwide. Spermatogenesis starts in the early fetus and completes after puberty, passing through different stages. Male infertility can result from primary or congenital, acquired, or idiopathic causes. The absence of sperm in semen, or azoospermia, results from non-obstructive causes (pretesticular and testicular), and post-testicular obstructive causes. Several medications such as antihypertensive drugs, antidepressants, chemotherapy, and radiotherapy could lead to impaired spermatogenesis and lead to a non-obstructive azoospermia. Spermatogonial stem cells (SSCs) are the basis for spermatogenesis and fertility in men. SSCs are characterized by their capacity to maintain the self-renewal process and differentiation into spermatozoa throughout the male reproductive life and transmit genetic information to the next generation. SSCs originate from gonocytes in the postnatal testis, which originate from long-lived primordial germ cells during embryonic development. The treatment of infertility in males has a poor prognosis. However, SSCs are viewed as a promising alternative for the regeneration of the impaired or damaged spermatogenesis. SSC transplantation is a promising technique for male infertility treatment and restoration of spermatogenesis in the case of degenerative diseases such as cancer, radiotherapy, and chemotherapy. The process involves isolation of SSCs and cryopreservation from a testicular biopsy before starting cancer treatment, followed by intra-testicular stem cell transplantation. In general, treatment for male infertility, even with SSC transplantation, still has several obstacles. The efficiency of cryopreservation, exclusion of malignant cells contamination in cancer patients, and socio-cultural attitudes remain major challenges to the wider application of SSCs as alternatives. Furthermore, there are limitations in experience and knowledge regarding cryopreservation of SSCs. However, the level of infrastructure or availability of regulatory approval to process and preserve testicular tissue makes them tangible and accurate therapy options for male infertility caused by non-obstructive azoospermia, though in their infancy, at least to date.

Germline stem cells in human

“…380 Prepubertal boys who suffer from gonadotoxic treatment under pediatric cancer circumstances, e.g., acute lymphoblastic leukemia and testicular cancer, might cause sterile for the rest of their life. 381 Autologous transplantation of SSCs or testicular tissue has been proposed as a strategy for fertility preservation and therapy [382][383][384][385] (Fig. 6).…”

Current and promising methods of idiopathic male infertility treatment

“…На сегодняшний день исследования проведены на грызунах и приматах. Концепция на данный момент не получила должной реализации своего потенциала, что связано с рядом серьезных препятствий [14,15].…”

The Role of Stem Cells and Their Derived Extracellular Vesicles in Restoring Female and Male Fertility

“…Moreover, bone marrow mesenchymal stem cell-derived EVs alleviated the testicular ischemia-reperfusion injury in the rat model through reduction in apoptosis [ 246 ] ( Table 2 ). Recently, we have reviewed the current clinical trials and animal models that use stem cells, or their derived EVs, and spermatogonial stem cells for the possible treatment of gonadotoxicity and the azoospermia cases [ 247 ].…”