Evaluation of carcinogenicity following intratesticular transplantation of autologous bone marrow-derived mesenchymal stem cells in non-obstructive azoospermia patients: a retrospective analysis
DOI:
https://doi.org/10.4081/aiua.2025.14330Keywords:
mesenchymal stem cells, non-obstructive, azoospermia, carcinogenicAbstract
Background: Non-obstructive azoospermia (NOA) cases may have severely deficient spermatogenesis and inadequate sperm production. Despite increasing clinical investigations emphasizing the safety of mesenchymal stem cell (MSC) therapy in NOA cases, no article has recently reviewed the adverse events and carcinogenicity after transplantation.
Objective: the study was conducted to evaluate the safety and potential carcinogenic effects of autologous human bone marrow- MSCs implanted into the testes of patients with NOA.
Methods: This retrospective cohort study was conducted throughout the period from January2017 to January 2022, encompassed 100 patients aged 20-40 years with primary infertility, with NOA for at least 2 years duration who had a confirmed diagnosis of NOA, based on two separate semen analyses showing azoospermia with centrifugation, conducted at least three months apart. Patients were submitted to intratesticular transplantation of autologous bone marrow-derived mesenchymal stem cells. Records of all participants were examined to acquire the demographic data of patients, laboratory investigations including β-HCG, ECG, AFP, LDH, and scrotal ultrasound examination.
Results: there is no significant malignancy or cancer occurrence post- MSCs therapy as indicated by the normal level of the tumor marker levels for LDH (183.4 ± 31.5) u/L, AFP (3.16 ± 1.6) ng/ ml, CEA (2.27 ± 1.1) ng/ ml, and β-HCG (0.95 ± 0.2) mIU/mL. Additionally, scrotal ultrasound showed no focal findings in all cases.
Conclusions: there is no carcinogenic effect of mesenchymal stem cells implanted into testes.
Downloads
References
1. Punjani N, Kang C, Lamb DJ, Schlegel PN. Current updates and future perspectives in the evaluation of azoospermia: a systematic review. Arab J Urol 2021; 19:206-14.
2. Arshad MA, Majzoub A, Esteves SC. Predictors of surgical sperm retrieval in non-obstructive azoospermia: summary of current literature. Int Urol Nephrol 2020; 52:2015-38.
3. Kim HJ, Park JS. Usage of human mesenchymal stem cells in cellbased therapy: advantages and disadvantages. Dev Reprod 2017; 31;21:1.
4. Chang Z, Zhu H, Zhou X, et al. Mesenchymal stem cells in preclinical infertility cytotherapy: a retrospective review. Stem Cells Int. 2021; 2021:8882368.
5. Wang Y, Yi H, Song Y. The safety of MSC therapy over the past 15 years: a meta-analysis. Stem Cell Res Ther 2021; 12:545.
6. Murray MJ, Huddart RA, Coleman N. The present and future of serum diagnostic tests for testicular germ cell tumours. Nat Rev Urol 2016; 13:715-25.
7. Zauner T, Heidler S, Lusuardi L, et al. Does Determining Tumor Markers from the Testicular Vein Enable Better Diagnosis and Prognosis? Urol Int. 2021; 105:264-8.
8. Oldenburg J, Berney DM, Bokemeyer C, et al. Testicular seminoma and non-seminoma: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann.Oncol 2022; 33:362-75.
9. Egan J, Salari K. Biomarkers in Testicular Cancer: Classic Tumor Markers and Beyond. Urol Clin North Am. 2023; 50:133-143.
10. Khizroeva J, Nalli C, Bitsadze V, et al. Infertility in women with systemic autoimmune diseases. Best Pract Res Clin Endocrinol Metab. 2019; 33:101369.
11. Minhas S, Bettocchi C, Boeri L, et al. EUA guidelines on male sexual and reproductive health: 2021 update on male infertility. Eur Urol 2021; 80:603-20.
12. Simon-Martinez C, Mailleux L, Ortibus E, et al. Combining constraint-induced movement therapy and action-observation training in children with unilateral cp: a randomized controlled trial. BMC Pediatr. 2018; 18:250.
13. Vaquero J, Zurita M, Rico MA, et al. Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline. Cytotherapy. 2018; 20:806-19.
14. Wang D, Li J, Zhang Y, et al. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Arthritis Res Ther 2014; 16:R79.
15. Alhefnawy MA, Elmorsy G, Bakry S, et al. Evaluation of human bone marrow mesenchymal stem cells in the treatment of non obstructive azoospermia. Arch Ital Urol Androl 2024; 96:12285.
16. Casiraghi F, Remuzzi G, Abbate M, Perico N. Multipotent mesenchymal stromal cell therapy and risk of malignancies. Stem Cell Rev Rep 2013; 9:65-79.
17. Zhankina R, Baghban N, Askarov M, et al. Mesenchymal stromal/stem cells and their exosomes for restoration of spermatogenesis in non-obstructive azoospermia: a systemic review. Stem Cell Res Ther. 2021;12:229.
18. Abougalala FM, Ali EK, Fayyad RM, et al. Mesenchymal stem cells for Busulfan-Induced Azoospermia: An experimental study. Int J Med Arts. 2022; 4:2319-24.
19. Cho IK, Easley CA. Recent developments in in vitro spermatogenesis and future directions. Reprod Med 2023; 4:215-32.
20. Baranovskii DS, Klabukov ID, Arguchinskaya NV, et al. Adverse events, side effects and complications in mesenchymal stromal cellbased therapies. Stem Cell Investig. 2022; 9:7.
21. Caplan AI. Adult mesenchymal stem cells: when, where, and how. Stem Cells Int. 2015; 2015:628767.
22. Zhankina R, Zhanbyrbekuly U, Askarov M, et al. Improving fertility in non-obstructive azoospermia: results from an autologous bone marrow-derived mesenchymal stromal/stem cell phase I clinical trial. Int. J Fertil Steril 2024; 18(Suppl 1):60.
23. Lalu MM, McIntyre L, Pugliese C, et al. Safe type of cell therapy with mesenchymal stromal cells (safe cell): a syst. review and meta-analysis of clinical trials. PloS One. 2012; 7:e47559.
24. Ning H, Yang F, Jiang M, et al. The correlation between co-transplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia. 2008; 22:593-9.
25. Li F, Xu J, Liu S. Cancer stem cells and neovascularization. Cells. 2021; 10:1070.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
