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.
In this work we reviewed the key antimitochondrial and antinuclear antibodies in primary biliary cholangitis -an autoimmune cholestatic disorder with destruction of intralobular biliary ductules. Since the discovery of antibodies to PDC-E2 component of cholangiocyte mitochondrial membrane, more than 60 antimitochindrial and antinuclear antibodies against various cellular components of cholangiocytes have been described to date, which have primary diagnostic and clinical value in identifying the disease progression and prognosis.
Stem cells are considered as new much promising therapeutic agents in treatment of male infertility due to their high differentiation potential and unlimited supply. In this review we summarized current views on application of mesenchymal stem cells in reproductive medicine.
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.
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