Improving Fertility in Non-Obstructive Azoospermia: Results from An Autologous Bone Marrow-Derived Mesenchymal Stromal/Stem Cell Phase I Clinical Trial
Zhankina R. Zhanbyrbekuly U. Askarov M. Zare A. Jafari N. Saipiyeva D. Sherkhanov R. Akhmetov D. Hashemi A. Farjam M. Tanideh N. Aflatoonian B. Mussin N.M. Kaliyev A.A. Sultangereyev Y. Baneshi H. Shirazi R. Mahdipour M. Bakhshalizadeh S. Rahmanifar F. Tamadon A.
June 2024Royan Institute (ACECR)
International Journal of Fertility and Sterility
2024#1860 - 70 pp.
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 non-obstructive 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 microsurgi-cal 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 re-generation 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.
Azoospermia , Clinical Trial , Mesenchymal Stem Cells , Protein-Protein Docking , Reproductive Techniques
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Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan
National Scientific Medical Center, Astana, Kazakhstan
Department of R&D Research, PerciaVista R&D Co, Shiraz, Iran
Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Pharmacology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Department of Reproductive Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Department of General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Surgery and Transplantation, Aktobe Medical Center, Aktobe, Kazakhstan
Department of Anatomy, School of Biomedical Sciences, Medicine & Health, UNSW Sydney, Sydney, Australia
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Reproductive Development, Murdoch Childrens Research Institute, Melbourne, VIC, Australia
Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Urology and Andrology
National Scientific Medical Center
Department of R&D Research
Noncommunicable Diseases Research Center
Stem Cells Technology Research Center
Department of Pharmacology
Stem Cell Biology Research Center
Department of Reproductive Biology
Department of Advanced Medical Sciences and Technologies
Department of General Surgery
Department of Surgery and Transplantation
Department of Anatomy
Stem Cell Research Center
Department of Applied Cell Sciences
Reproductive Development
Department of Paediatrics
Department of Basic Sciences
Department of Natural Sciences
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