Document Type : Original Article
Authors
1
Department of Urology and Andrology, Astana Medical University, Astana, Kazakhstan
2
Department of Urology and Andrology, Astana Medical University, Nur-Sultan, Kazakhstan
3
National Scientific Medical Center, Astana, Kazakhstan
4
PerciaVista R&D Co. Shiraz, Iran
5
Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
6
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
7
Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
8
General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
9
Department of Anatomy, School of Medical Sciences, Medicine, UNSW Sydney, PO Box 2052, Sydney, Australia
10
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
11
Reproductive Development, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
12
Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
13
Department for Scientific Work, West-Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
10.22074/ijfs.2023.2005045.1480
Abstract
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.
Participants: 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.
Methods: 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 testos-terone and inhibin B levels, elevated sperm concentration, and reduced levels of follicle-stimulating hor-mone (FSH), luteinizing hormone (LH), and prolactin. Notably, in nine patients (22.5%) previously diag-nosed 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 poten-tial 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 sper-matogenesis. 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.
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