Title of article :
Improving Fertility in Non-obstructive Azoospermia: Results from an Autologous Bone Mar-row-Derived Mesenchymal Stromal/Stem Cell Phase I Clinical Trial
Author/Authors :
Zhankina ، Rano Department of Urology and Andrology - Astana Medical University , Zhanbyrbekuly ، Ulanbek Department of Urology and Andrology - Astana Medical University , Askarov ، Manarbek National Scientific Medical Center , Zare ، Afshin Department of R D Research - PerciaVista R D Co. , Jafari ، Nazanin Department of R D Research - PerciaVista R D Co. , Saipiyeva ، Dana Department of Urology and Andrology - Astana Medical University , Sherkhanov ، Ravil Department of Urology and Andrology - Astana Medical University , Akhmetov ، Daniyar Department of Urology and Andrology - Astana Medical University , Hashemi ، Alireza Department of R D Research - PerciaVista R D Co. , Farjam ، Mojtaba Noncommunicable Diseases Research Center - Fasa University of Medical Sciences , Tanideh ، Nader Department of R D Research - PerciaVista R D Co. , Aflatoonian ، Behrouz Department of Reproductive Biology, Department of Advanced Medical Sciences and Technologies - Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, School of Medicine, School of Paramedicine - Shahid Sadoughi University of Medical Sciences , Mussin ، Nadiar Maratovich Department of General Surgery - West Kazakhstan Marat Ospanov Medical University , Kaliyev ، Asset Askerovich Department of General Surgery - West Kazakhstan Marat Ospanov Medical University , Sultangereyev ، Yerlan Department of General Surgery - West Kazakhstan Marat Ospanov Medical University , Baneshi ، Hanieh Department of R D Research - PerciaVista R D Co. , Shirazi ، Reza Department of Anatomy - School of Biomedical Sciences, Medicine Health - University of New South Wales (UNSW) Sydney , Mahdipour ، Mahdi Department of Applied Cell Sciences - Stem Cell Research Center, Faculty of Advanced Medical Sciences - Tabriz University of Medical Sciences , Bakhshalizadeh ، Shabnam Reproductive Development - Murdoch Children s Research Institute , Rahmanifar ، Farhad Department of Basic Sciences - School of Veterinary Medicine - Shiraz University , Tamadon ، Amin Department of R D Research - PerciaVista R D Co.
Abstract :
Background: In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approachutilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructiveazoospermia (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 patientsundergoing 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 microsurgicaltesticular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before andsix months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactionsbetween 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 Blevels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), andprolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia beforetreatment, 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 potentialbinding 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 regenerationof seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings supportthe safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus onthe achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).
Keywords :
Azoospermia , Clinical Trial , Mesenchymal Stem Cells , Protein , Protein Docking , Reproductive Techniques
Journal title :
International Journal of Fertility and Sterility
Journal title :
International Journal of Fertility and Sterility