Non-obstructive azoospermia treatment by autologous bone marrow-derived mesenchymal stromal/stem cells: a non-randomized, open-label phase I clinical trial

Abstract Background Non-obstructive azoospermia (NOA) is considered a cause of male infertility that does not respond to drug therapy. Mesenchymal stromal/stem cell therapy has been recognized as a new fertility treatment option. Here, we propose an approach in which autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) are used in NOA treatment for the first time. Methods This non-randomized, open-label phase I clinical trial screened 19 participants undergoing NOA treatment by autologous BM-MSCs. The bone marrow was harvested by percutaneous aspiration from the anterior superior iliac spine. After bone marrow aspiration and cultivation of BM-MSCs, they were autotransplanted into the testicular network with microsurgical testicular sperm extraction (microTESE). Patients were evaluated for semen analysis and hormonal levels of follicle-stimulating hormone (FSH), total testosterone, luteinizing hormone (LH), inhibin B, and prolactin before and six months after injection of BM-MSCs. Results BM-MSCs were characterized under a light microscope, as well as by the expression of markers CD73, CD105, CD117, and CD105+34+ MSCs. The results showed that this autotransplantation is safe, the patients did not experience deterioration, allergic reactions, suppuration of wounds, complications from the cardiovascular, respiratory, nervous, urinary and circulatory systems. As noted, the percentage of testosterone, inhibin B and sperm concentration increased, while the percentage of FSH, LH and prolactin decreased after treatment. In four patients (21.1%). who were previously diagnosed with secondary infertility, but during the following years there were no spermatozoa in the spermogram six months after treatment, single spermatozoa were found in the spermograms, which underwent cryopreservation for subsequent preparation for IVF. Based on the hormonal profile before and after six months of treatment, four out of 19 patients were successfully treated with the proposed method without any complications. Conclusion The BM-MSCs autotransplantation into the testicular networks with microTESE in NOA patients induced regeneration of the seminiferous tubules, and also regulate the spermatogenesis cycle hormones. Therefore, autologous BM-MSCs is safe and effective in the treatment of NAO.