Human Spermatogonial Stem Cell Culture In Vitro: A Review of New Materials and Recent Advances

نویسندگان

1 Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Applied Physiology Research Center, Cardiovascular Research Institute, Department of Anatomical Sciences and Reproductive Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Laboratory Sciences, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

doi
10.22074/cellj.2025.2034670.1616
چکیده

There is a high prevalence of infertility worldwide (17.5% of the adult population), with male factors comprising 40% ofcases. Therefore, research is vital for addressing the challenges faced by infertile men. Innovative methods, diagnosis, andtreatment are necessary for male infertility, and stem cell science has brought about significant breakthroughs in its treatment.Spermatogonial stem cells (SSCs) play a crucial role in maintaining reproductive function in males, and advancements intheir in vitro culture show promising developments. An array of specific growth factors and compounds that include epidermalgrowth factor (EGF), leukaemia inhibitory factor (LIF), glial cell line-derived neurotrophic factor (GDNF), basic fibroblastgrowth factor (bFGF), stem cell factor (SCF), vitamin A/retinol, testosterone, and follicle stimulating hormone (FSH) areapplied to natural or artificial surfaces to mimic the testicular niche to preserve SSCs viability and induce their differentiation.These media should maintain self-renewal ability, continuously generate daughter spermatogonia, and differentiate intospermatozoa. However, several limitations and challenges exist despite the significant progress in SSC culture techniques.One limitation is the difficulty in fully replicating the intricate in vivo testicular niche. This complex microenvironment that includesthe dynamic interplay of somatic cells, hormones, growth factors, and external matrix components is crucial for supportingSSC self-renewal and differentiation. Currently, in vitro systems do not adequately replicate this microenvironment, resultingin suboptimal SSC maintenance and inconsistent differentiation outcomes. This might be a key challenge for achievingcomplete and functional spermatogenesis in vitro. We review the foundational concepts and recent breakthroughs in in vitrospermatogenesis, focusing particularly on studies in human systems from the past twenty years. As a conclusion from thisreview article, developing a defined culture system that accurately mimics the in vivo niche is crucial for maintaining thefunctional properties of spermatogonial stem cells. The establishment of such a reliable platform is an essential prerequisitefor translating in vitro spermatogenesis into clinical applications for treating infertility.