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https://doi.org/10.18502/wkmj.v66i1.15679
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Farhad Rahmanifar
Farhad Rahmanifar
Department of Basic Sciences, Shiraz University, Shiraz, Iran
Published Date
- Mar 14, 2024
Mesenchymal Stem Cell Therapy for Azoospermia: Navigating Differentiation Challenges and Charting Future Frontiers in Male Fertility Treatment
Abstract
This minireview explores the current landscape of stem cell therapy for azoospermia, focusing on the potential and challenges associated with Mesenchymal Stem Cells (MSCs). The discussion encompasses the precise regulation of MSC differentiation, safety considerations, and ethical implications. Recent advancements in optimizing differentiation protocols, improving engraftment efficiency, and ongoing clinical trials are highlighted. Despite the hurdles, MSCs emerge as a promising avenue for male infertility treatment. The conclusion emphasizes the necessity for continued research and clinical trials to unlock the full potential of MSC therapy in addressing the complexities of azoospermia.
References
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[2] Qian C, Meng Q, Lu J, Zhang L, Li H, Huang B. Human amnion mesenchymal stem cells restore spermatogenesis in mice with busulfan-induced testis toxicity by inhibiting apoptosis and oxidative stress. Stem Cell Res Ther. 2020;11(1):290.
[3] Zhankina R, Baghban N, Askarov M, Saipiyeva D, Ibragimov A, Kadirova B, 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(1):229.
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[5] Tamadon A, Mehrabani D, Rahmanifar F, Jahromi AR, Panahi M, Zare S, et al. Induction of spermatogenesis by bone marrow-derived mesenchymal stem cells in busulfan-induced azoospermia in hamster. Int J Stem Cells. 2015;8(2):134-45.
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[10] Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, et al. Ethical and safety issues of stem cell-based therapy. Int J Med Sci. 2018;15(1):36-45.
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[14] Teves ME, Roldan ERS, Krapf D, Strauss JF, III, Bhagat V, Sapao P. Sperm differentiation: The role of trafficking of proteins. Int J Mol Sci. 2020;21(10).
[15] Makela JA, Hobbs RM. Molecular regulation of spermatogonial stem cell renewal and differentiation. Reproduction. 2019;158(5):R169-R87.
[16] Tanga BM, Qamar AY, Raza S, Bang S, Fang X, Yoon K, et al. Semen evaluation: Methodological advancements in sperm quality-specific fertility assessment - A review. Anim Biosci. 2021;34(8):1253-70.
[17] Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal stem cells for regenerative medicine. Cells. 2019;8(8).
[18] Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci. 2020;77(14):2771-94.
[19] Liska MG, Crowley MG, Borlongan CV. Regulated and unregulated clinical trials of stem cell therapies for stroke. Transl Stroke Res. 2017;8(2):93-103.
[20] Merimi M, El-Majzoub R, Lagneaux L, Moussa Agha D, Bouhtit F, Meuleman N, et al. The therapeutic potential of mesenchymal stromal cells for regenerative medicine: Current knowledge and future understandings. Front Cell Dev Biol. 2021;9:661532.
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[22] Burlacu A. Tracking the mesenchymal stem cell fate after transplantation into the infarcted myocardium. Curr Stem Cell Res Ther. 2013;8(4):284-91.
[23] Jovic D, Yu Y, Wang D, Wang K, Li H, Xu F, et al. A brief overview of global trends in MSC-based cell therapy. Stem Cell Rev Rep. 2022;18(5):1525-45.
[24] Wu Y, Shum HCE, Wu K, Vadgama J. From interaction to intervention: How mesenchymal stem cells affect and target triple-negative breast cancer. Biomedicines. 2023;11(4).
[25] Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): Mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol. 2019;10:1191.
[26] Nowzari F, Wang H, Khoradmehr A, Baghban M, Baghban N, Arandian A, et al. Threedimensional imaging in stem cell-based researches. Front Vet Sci. 2021;8:657525.
[27] Neri S. Genetic stability of mesenchymal stromal cells for regenerative medicine applications: A fundamental biosafety aspect. Int J Mol Sci. 2019;20(10).
[28] Omole AE, Fakoya AOJ, Nnawuba KC, Haider KH. Common ethical considerations of human-induced pluripotent stem cell research. Handbook of Stem Cell Therapy: Springer; 2022. p. 1-17.
[29] Rubeis G, Steger F. Risks and benefits of human germline genome editing: An ethical analysis. Asian Bioeth Rev. 2018;10(2):133-41.
[30] Kadam RA. Informed consent process: A step further towards making it meaningful! Perspect Clin Res. 2017;8(3):107-12.
[31] Mehta P, Zimba O, Gasparyan AY, Seiil B, Yessirkepov M. Ethics committees: Structure, roles, and issues. J Korean Med Sci. 2023;38(25):e198.
[32] Cocuzza M, Alvarenga C, Pagani R. The epidemiology and etiology of azoospermia. Clinics (Sao Paulo). 2013;68 Suppl 1(Suppl 1):15-26.
[33] Dunn CM, Kameishi S, Grainger DW, Okano T. Strategies to address mesenchymal stem/stromal cell heterogeneity in immunomodulatory profiles to improve cell-based therapies. Acta Biomater. 2021;133:114-25.
[34] Lira FNTN. Hormonal treatment for men with non-obstructive azoospermia: Too many rationales, too little data. Int Braz J Urol. 2022;48(3):482-4.
[35] Roshandel E, Mehravar M, Nikoonezhad M, Alizadeh AM, Majidi M, Salimi M, et al. Cell-based therapy approaches in treatment of non-obstructive azoospermia. Reprod Sci. 2023;30(5):1482-94.
[36] Zhou T, Yuan Z, Weng J, Pei D, Du X, He C, et al. Challenges and advances in clinical applications of mesenchymal stromal cells. J Hematol Oncol. 2021;14(1):24.
[37] Hsiao CH, Ji AT, Chang CC, Cheng CJ, Lee LM, Ho JH. Local injection of mesenchymal stem cells protects testicular torsion-induced germ cell injury. Stem Cell Res Ther. 2015;6(1):113.
[38] Khatami F, Hassanzad M, Nikfar S, Guitynavard F, Karimaee S, Tamehri Zadeh SS, et al. The importance of personalized medicine in urological cancers. J Diabetes Metab Disord. 2022;21(1):841-52.
[39] Andrade DL, Viana MC, Esteves SC. Differential diagnosis of azoospermia in men with infertility. J Clin Med. 2021;10(14):3144.
[40] Patel SA, King CC, Lim PK, Habiba U, Dave M, Porecha R, et al. Personalizing stem cell research and therapy: The arduous road ahead or missed opportunity? Curr Pharmacogenomics Person Med. 2010;8(1):25-36.
[41] Krist AH, Tong ST, Aycock RA, Longo DR. Engaging patients in decision-making and behavior change to promote prevention. Stud Health Technol Inform. 2017;240:284- 302.
[2] Qian C, Meng Q, Lu J, Zhang L, Li H, Huang B. Human amnion mesenchymal stem cells restore spermatogenesis in mice with busulfan-induced testis toxicity by inhibiting apoptosis and oxidative stress. Stem Cell Res Ther. 2020;11(1):290.
[3] Zhankina R, Baghban N, Askarov M, Saipiyeva D, Ibragimov A, Kadirova B, 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(1):229.
[4] Abdelaal NE, Tanga BM, Abdelgawad M, Allam S, Fathi M, Saadeldin IM, et al. Cellulartherapy via spermatogonial stem cells for treating impaired spermatogenesis, nonobstructive azoospermia. Cells. 2021;10(7).
[5] Tamadon A, Mehrabani D, Rahmanifar F, Jahromi AR, Panahi M, Zare S, et al. Induction of spermatogenesis by bone marrow-derived mesenchymal stem cells in busulfan-induced azoospermia in hamster. Int J Stem Cells. 2015;8(2):134-45.
[6] Ibtisham F, Honaramooz A. Spermatogonial stem cells for in vitro spermatogenesis and in vivo restoration of fertility. Cells. 2020;9(3).
[7] Cho IK, Easley CA. Recent developments in in vitro spermatogenesis and future directions. Reproductive Medicine. 2023;4(3):215-32.
[8] Chao HH, Zhang Y, Dong PY, Gurunathan S, Zhang XF. Comprehensive review on the positive and negative effects of various important regulators on male spermatogenesis and fertility. Front Nutr. 2022;9:1063510.
[9] Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, et al. Stem cellbased therapy for human diseases. Signal Transduct Target Ther. 2022;7(1):272.
[10] Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, et al. Ethical and safety issues of stem cell-based therapy. Int J Med Sci. 2018;15(1):36-45.
[11] Cervan-Martin M, Tuttelmann F, Lopes AM, Bossini-Castillo L, Rivera-Egea R, Garrido N, et al. Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility. Commun Biol. 2022;5(1):1220.
[12] Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z. Stem cells: Past, present, and future. Stem Cell Res Ther. 2019;10(1):68.
[13] Fayezi S, Fayyazpour P, Norouzi Z, Mehdizadeh A. Strategies for mammalian mesenchymal stem cells differentiation into primordial germ cell-like cells: A review. Cell J. 2022;24(8):434-41.
[14] Teves ME, Roldan ERS, Krapf D, Strauss JF, III, Bhagat V, Sapao P. Sperm differentiation: The role of trafficking of proteins. Int J Mol Sci. 2020;21(10).
[15] Makela JA, Hobbs RM. Molecular regulation of spermatogonial stem cell renewal and differentiation. Reproduction. 2019;158(5):R169-R87.
[16] Tanga BM, Qamar AY, Raza S, Bang S, Fang X, Yoon K, et al. Semen evaluation: Methodological advancements in sperm quality-specific fertility assessment - A review. Anim Biosci. 2021;34(8):1253-70.
[17] Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal stem cells for regenerative medicine. Cells. 2019;8(8).
[18] Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci. 2020;77(14):2771-94.
[19] Liska MG, Crowley MG, Borlongan CV. Regulated and unregulated clinical trials of stem cell therapies for stroke. Transl Stroke Res. 2017;8(2):93-103.
[20] Merimi M, El-Majzoub R, Lagneaux L, Moussa Agha D, Bouhtit F, Meuleman N, et al. The therapeutic potential of mesenchymal stromal cells for regenerative medicine: Current knowledge and future understandings. Front Cell Dev Biol. 2021;9:661532.
[21] Faden VB, Day NL, Windle M, Windle R, Grube JW, Molina BS, et al. Collecting longitudinal data through childhood, adolescence, and young adulthood: methodological challenges. Alcohol Clin Exp Res. 2004;28(2):330-40.
[22] Burlacu A. Tracking the mesenchymal stem cell fate after transplantation into the infarcted myocardium. Curr Stem Cell Res Ther. 2013;8(4):284-91.
[23] Jovic D, Yu Y, Wang D, Wang K, Li H, Xu F, et al. A brief overview of global trends in MSC-based cell therapy. Stem Cell Rev Rep. 2022;18(5):1525-45.
[24] Wu Y, Shum HCE, Wu K, Vadgama J. From interaction to intervention: How mesenchymal stem cells affect and target triple-negative breast cancer. Biomedicines. 2023;11(4).
[25] Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): Mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol. 2019;10:1191.
[26] Nowzari F, Wang H, Khoradmehr A, Baghban M, Baghban N, Arandian A, et al. Threedimensional imaging in stem cell-based researches. Front Vet Sci. 2021;8:657525.
[27] Neri S. Genetic stability of mesenchymal stromal cells for regenerative medicine applications: A fundamental biosafety aspect. Int J Mol Sci. 2019;20(10).
[28] Omole AE, Fakoya AOJ, Nnawuba KC, Haider KH. Common ethical considerations of human-induced pluripotent stem cell research. Handbook of Stem Cell Therapy: Springer; 2022. p. 1-17.
[29] Rubeis G, Steger F. Risks and benefits of human germline genome editing: An ethical analysis. Asian Bioeth Rev. 2018;10(2):133-41.
[30] Kadam RA. Informed consent process: A step further towards making it meaningful! Perspect Clin Res. 2017;8(3):107-12.
[31] Mehta P, Zimba O, Gasparyan AY, Seiil B, Yessirkepov M. Ethics committees: Structure, roles, and issues. J Korean Med Sci. 2023;38(25):e198.
[32] Cocuzza M, Alvarenga C, Pagani R. The epidemiology and etiology of azoospermia. Clinics (Sao Paulo). 2013;68 Suppl 1(Suppl 1):15-26.
[33] Dunn CM, Kameishi S, Grainger DW, Okano T. Strategies to address mesenchymal stem/stromal cell heterogeneity in immunomodulatory profiles to improve cell-based therapies. Acta Biomater. 2021;133:114-25.
[34] Lira FNTN. Hormonal treatment for men with non-obstructive azoospermia: Too many rationales, too little data. Int Braz J Urol. 2022;48(3):482-4.
[35] Roshandel E, Mehravar M, Nikoonezhad M, Alizadeh AM, Majidi M, Salimi M, et al. Cell-based therapy approaches in treatment of non-obstructive azoospermia. Reprod Sci. 2023;30(5):1482-94.
[36] Zhou T, Yuan Z, Weng J, Pei D, Du X, He C, et al. Challenges and advances in clinical applications of mesenchymal stromal cells. J Hematol Oncol. 2021;14(1):24.
[37] Hsiao CH, Ji AT, Chang CC, Cheng CJ, Lee LM, Ho JH. Local injection of mesenchymal stem cells protects testicular torsion-induced germ cell injury. Stem Cell Res Ther. 2015;6(1):113.
[38] Khatami F, Hassanzad M, Nikfar S, Guitynavard F, Karimaee S, Tamehri Zadeh SS, et al. The importance of personalized medicine in urological cancers. J Diabetes Metab Disord. 2022;21(1):841-52.
[39] Andrade DL, Viana MC, Esteves SC. Differential diagnosis of azoospermia in men with infertility. J Clin Med. 2021;10(14):3144.
[40] Patel SA, King CC, Lim PK, Habiba U, Dave M, Porecha R, et al. Personalizing stem cell research and therapy: The arduous road ahead or missed opportunity? Curr Pharmacogenomics Person Med. 2010;8(1):25-36.
[41] Krist AH, Tong ST, Aycock RA, Longo DR. Engaging patients in decision-making and behavior change to promote prevention. Stud Health Technol Inform. 2017;240:284- 302.