Improving Fertility in Non-obstructive Azoospermia: Results from an Autologous Bone Mar-row-Derived Mesenchymal Stromal/Stem Cell Phase I Clinical Trial.

Autor: Zhankina R; Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan., Zhanbyrbekuly U; Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan., Askarov M; National Scientific Medical Center, Astana, Kazakhstan., Zare A; Department of R&D Research, PerciaVista R&D Co., Shiraz, Iran., Jafari N; Department of R&D Research, PerciaVista R&D Co., Shiraz, Iran., Saipiyeva D; Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan., Sherkhanov R; Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan., Akhmetov D; Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan., Hashemi A; Department of R&D Research, PerciaVista R&D Co., Shiraz, Iran., Farjam M; Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran., Tanideh N; Department of R&D Research, PerciaVista R&D Co., Shiraz, 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., Aflatoonian B; 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., Mussin NM; Department of General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan., Kaliyev AA; Department of General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan., Sultangereyev Y; Department of General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.; Department of Surgery and Transplantation, Aktobe Medical Center, Aktobe, Kazakhstan., Baneshi H; Department of R&D Research, PerciaVista R&D Co., Shiraz, Iran., Shirazi R; Department of Anatomy, School of Biomedical Sciences, Medicine & Health, UNSW Sydney, Sydney, Australia., Mahdipour M; 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., Bakhshalizadeh S; Reproductive Development, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia., Rahmanifar F; Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran., Tamadon A; Department of R&D Research, PerciaVista R&D Co., Shiraz, Iran.; Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan. Email: amintamaddon@yahoo.com.
Jazyk: angličtina
Zdroj: International journal of fertility & sterility [Int J Fertil Steril] 2024 Jul 13; Vol. 18 (Suppl 1), pp. 60-70. Date of Electronic Publication: 2024 Jul 13.
DOI: 10.22074/ijfs.2023.2005045.1480
Abstrakt: 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).
Databáze: MEDLINE
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