RESUMEN
BACKGROUND: In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approach utilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructive azoospermia (NOA). Additionally, we aimed to assess the feasibility and safety of this approach. MATERIALS AND METHODS: We recruited 80 participants in this non-randomized, open-label clinical trial, including patients undergoing NOA treatment using autologous BM-MSCs (n=40) and those receiving hormone therapy as a control group (n=40). Detailed participant characteristics, such as age, baseline hormonal profiles, etiology of NOA, and medical history, were thoroughly documented. Autotransplantation of BM-MSCs into the testicular network was achieved using microsurgical testicular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before and six months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactions between exosomes secreted from BM-MSCs and receptors present in human seminiferous tubule cells. RESULTS: Our results revealed significant improvements following treatment, including increased testosterone and inhibin B levels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia before treatment, the proposed approach yielded successful outcomes, as indicated by hormonal profile changes over six months. Importantly, these improvements were achieved without complications. Additionally, our in-silico analysis identified potential binding interactions between the protein content of BM-MSC-derived exosomes and receptors integral to spermatogenesis. CONCLUSION: Autotransplantation of BM-MSCs into the testicular network using microTESE in NOA patients led to the regeneration of seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings support the safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus on the achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).
RESUMEN
Stem cells have been introduced as new promising therapeutic agents in treatment of degenerative diseases because of having high differentiation potential while maintaining the ability to self-replicate and retaining features of their source cells. Among different type of cell therapies, mesenchymal stromal/stem cell (MSC) therapy is being increasingly developed as a new way to treat structural defects that need to be repaired and regenerated. Non-obstructive azoospermia (NOA) is a reproductive disease in men that causes infertility in 10% of infertile men. Based on in vitro studies, MSCs from different tissue sources have been differentiated into germ cells or gamete progenitor cells by simple methods in both male and female. On the other hand, the therapeutic effects of MSCs have been evaluated for the treatment of NOA animal models created by chemical or surgical compounds. The results of these studies confirmed successful allotransplantation or xenotransplantation of MSCs in the seminiferous tubules. As well, it has been reported that exosomes secreted by MSCs are able to induce the process of spermatogenesis in the testes of infertile animal models. Despite numerous advances in the treatment of reproductive diseases in men and women with the help of MSCs or their exosomes, no clinical trial has been terminated on the treatment of NOA. This systematic review attempts to investigate the possibility of MSC therapy for NOA in men.