Spermatogenesis after transplantation of adipose tissue-derived mesenchymal stem cells in busulfan-induced azoospermic hamster

Document Type : Original Article

Authors

1 Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

3 Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

4 Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

5 Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran

6 Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Objective(s): Adipose tissue-derived mesenchymal stem cells (AT-MSCs) with more potent immunomodulatory effects, greater proliferative potential and secretion of growth factors and cytokines in comparison with bone marrow derived MSCs are more appropriate for cell therapy. The aims of the present study were to evaluate the histomorphometric effect of AT-MSCs allotransplantation on regeneration of germinal layer cells of seminiferous tubules in busulfan-induced azoospermic hamsters.
Materials and Methods: In the present experimental case-control study, AT-MSCs were isolated from adipose tissue of two female and six male donor albino hamsters, and testes of the males were simultaneously used as negative control group. Six mature male recipient hamsters received two doses of busulfan with three weeks interval to stop endogenous spermatogenesis. Right testis of hamsters was intratubular injected with AT-MSCs via efferent duct 35 days after induction of azoospermia and was used as cell therapy group. The left testis without cell therapy was served as azoospermia group.
Results: After 35 days, testes and epididymis in all groups were removed for histological evaluation. Histomorphometric analyses of AT-MSCs-treated testes and epididymis showed that the epithelial tissue of seminiferous tubules was normally repaired in most cell-treated seminiferous tubules, and spermatozoa were present in epididymis tubes in comparison with intact testes. The untreated seminiferous tubules and epididymis tubes of azoospermia group were empty.
Conclusion: Allotransplanted AT-MSCs could successfully induce spermatogenesis in azoospermic seminiferous tubules of hamster. Therefore, AT-MSCs can be suggested as an attractive candidate in cell transplantation of azoospermia.

Keywords

Main Subjects


1. Vassena R, Eguizabal C, Heindryckx B, Sermon K, Simon C, van Pelt A, et al. Stem cells in reproductive medicine: ready for the patient? Hum Reprod 2015;30:2014-2021.
2. Gudeloglu A, Parekattil SJ. Update in the evaluation of the azoospermic male. Clinics 2013;68:27-34.
3. O’Brien KLF, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril 2010;93:1-12.
4. Hajihoseini M, Vahdati A, Ebrahim Hosseini S, Mehrabani D, Tamadon A. Induction of spermatogenesis after stem cell therapy of azoospermic guinea pigs. Vet Arhiv 2017;87:333-350.
5. Mehrabani D, Hassanshahi MA, Tamadon A, Zare S, Keshavarz S, Rahmanifar F, et al. Adipose tissue-derived mesenchymal stem cells repair germinal cells of seminiferous tubules of busulfan-induced azoospermic rats. J Hum Reprod Sci 2015;8:103-110.
6. Mehrabani D, Rabiee M, Tamadon A, Zare S, Jahromi IR, Dianatpour M, et al. The growth kinetic, differentiation properties, karyotyping, and characterization of adipose tissue-derived stem cells in hamster. Comp Clin Pathol 2016;25:1017-1022.
7. Shaterzadeh-Yazdi H, Mehrabani D, Khodakaram-Tafti A, Dianatpour M, Zare SH, Tamadon A, et al. Osteogenic potential of subcutaneous adipose-derived stem cells in a rabbit model. Online J Vet Res 2015;19:436-445.
8. Mehrabani D, Rahmanifar F, Mellinejad M, Tamadon A, Dianatpour M, Zare S, et al. Isolation, culture, characterization, and adipogenic differentiation of heifer endometrial mesenchymal stem cells. Comp Clin Pathol 2015;24:1159-1164.
9. Tamadon A, Mehrabani D, Zarezadeh Y, Rahmanifar F, Dianatpour M, Zare S. Caprine endometrial mesenchymal stromal stem cell: multi-lineage potential, characterization and growth kinetics in breeding and anestrous stages. Vet Med Int 2017;2017:5052801.
10. Mehrabani D, Mahdiyar P, Torabi K, Robati R, Zare S, Dianatpour M, et al. Growth kinetics and characterization of human dental pulp stem cells: Comparison between third molar and first premolar teeth. J Clin Exp Dent 2017;9:e172-e177.
11. Khodabandeh Z, Vojdani Z, Talaei-Khozani T, Jaberipour M, Hosseini A, Bahmanpour S. Comparison of the expression of hepatic genes by human Wharton’s Jelly mesenchymal stem cells cultured in 2D and 3D Collagen culture systems. Iran J Med Sci 2016;41:28-36.
12. Mehrabani D, Bahrami Nazarabadi R, Dianatpour M, Vahdati A, Tamadon A, Kasraeian M, et al. Growth kinetics, characterization and plasticity of human menstrual blood stem cells. Iran J Med Sci 2015;41:132-139.
13. Mehrabani D, Khodakaram-Tafti A, Asadi-Yousefabad SL, Dianatpour M, Zare S, Tamadon A, et al. Effect of age and passage on canine bone marrow derived mesenchymal stem cells. Online J Vet Res 2015;19:663-671.
14. Khajehahmadi Z, Mehrabani D, Ashraf MJ, Rahmanifar F, Tanideh N, Tamadon A, et al. Healing effect of conditioned media from bone marrow-derived stem cells in thioacetamide-induced liver fibrosis of rat. J Med Sci 2016;16:7-15.
15. Tamadon A, Mehrabani D, Rahmanifar F, Raayat Jahromi A, 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;8:134-145.
16. Rahmanifar F, Tamadon A, Mehrabani D, Zare S, Abasi S, Keshavarz S, et al. Histomorphometric evaluation of treatment of rat azoospermic seminiferous tubules by allotransplantation of bone marrow-derived mesenchymal stem cells. Iran J Basic Med Sci 2016;19:653-661.
17. Aliborzi G, Vahdati A, Mehrabani D, Ebrahim Hosseini S, Tamadon A. Isolation, characterization and growth kinetic comparison of bone marrow and adipose tissue mesenchymal stem cells of Guinea pig. Int J Stem Cells 2015;9:115-123.
18. Razeghian Jahromi I, Mehrabani D, Mohammadi A, Dianatpour M, Tamadon A, Zare S, et al. The effect of fetal rat brain extract on morphology of bone marrow-derived mesenchymal stem cells. Comp Clin Pathol 2016;25:343-349.
19. Razeghian Jahromi I, Mehrabani D, Mohammadi A, Ghahremani Seno MM, Dianatpour M, Zare S, et al. Emergence of signs of neural cells after exposure of bone marrow-derived mesenchymal stem cells to fetal brain extract. Iran J Basic Med Sci 2017;20:301-307.
20. Danner S, Kajahn J, Geismann C, Klink E, Kruse C. Derivation of oocyte-like cells from a clonal pancreatic stem cell line. Mol Hum Reprod 2007;13:11-20.
21. Moreno I, Míguez-Forjan JM, Simón C. Artificial gametes from stem cells. Clin Exp Reprod Med 2015;42:33-44.
22. Bucay N, Yebra M, Cirulli V, Afrikanova I, Kaido T, Hayek A, et al. A novel approach for the derivation of putative primordial germ cells and Sertoli cells from human embryonic stem cells. Stem Cells 2009;27:68-77.
23. Yang S, Bo J, Hu H, Guo X, Tian R, Sun C, et al. Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules. Cell Prolif 2012;45:91-100.
24. Nayernia K, Lee JH, Drusenheimer N, Nolte J, Wulf G, Dressel R, et al. Derivation of male germ cells from bone marrow stem cells. Lab Invest 2006;86:654-663.
25. Li C-y, Wu X-y, Tong J-b, Yang X-x, Zhao J-l, Zheng Q-f, et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem cell Res Ther 2015;6:1-13.
26. Suttorp M, Millot F. Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. Hematology Am Soc Hematol Educ Program 2010;2010:368-376.
27. Panahi M, Karimaghai N, Rahmanifar F, Tamadon A, Vahdati A, Mehrabani D, et al. Stereological evaluation of testes in busulfan-induced infertility of hamster. Comp Clin Pathol 2014;24:1051-1056.
28. Ford J, Carnes K, Hess RA. Ductuli efferentes of the male Golden Syrian hamster reproductive tract. Andrology 2014;2:510-520.
29. Ilio KY, Hess RA. Structure and function of the ductuli efferentes: a review. Microsc Res Tech 1994;29:432-467.
30. Van Saen D, Goossens E, De Block G, Tournaye H. Bone marrow stem cells transplanted to the testis of sterile mice do not differentiate into spermatogonial stem cells and have no protective effect on fertility. Fertil Steril 2009;91:1549-1552.
31. Lue YH, Erkkila K, Liu PY, Ma K, Wang C, Hikim AS, et al. Fate of bone marrow stem cells transplanted into the testis: potential implication for men with testicular failure. Am J Pathol 2007;170:899-908.
32. Monsefi M, Fereydouni B, Rohani L, Talaei T. Mesenchymal stem cells repair germinal cells of seminiferous tubules of sterile rats. Iran J Reprod Med 2013;11:537.
33. Zahkook SA, Atwa A, Shahat M, Mansour AM, Bakry S. Mesenchymal stem cells restore fertility in induced azoospermic rats following chemotherapy administration. J Reprod Infertil 2014;5:50-57.
34. Zhang D, Liu X, Peng J, He D, Lin T, Zhu J, et al. Potential spermatogenesis recovery with bone marrow mesenchymal stem cells in an azoospermic rat model. Int J Mol Sci 2014;15:13151-13165.
35. Sabbaghi MA, Bahrami AR, Feizzade B, Kalantar SM, Matin MM, Kalantari M, et al. Trial evaluation of bone marrow derived mesenchymal stem cells (MSCs) transplantation in revival of spermatogenesis in testicular torsion. Middle East Fertil Soc J 2012;17:243-249.
36. Cakici C, Buyrukcu B, Duruksu G, Haliloglu AH, Aksoy A, Isık A, et al. Recovery of fertility in azoospermia rats after injection of adipose-tissue-derived mesenchymal stem cells: the sperm generation. BioMed Res Int 2013;2013:529589.
37. Chen H, Tang QL, Wu XY, Xie LC, Lin LM, Ho GY, et al. Differentiation of human umbilical cord mesenchymal stem cells into germ-like cells in mouse seminiferous tubules. Mol Med Rep 2015;12:819-828.
38. Zhu Y, Hu H-L, Li P, Yang S, Zhang W, Ding H, et al. Generation of male germ cells from induced pluripotent stem cells (iPS cells): an in vitro and in vivo study. Asian J Androl 2012;14:574-579.
39. Xie L, Lin L, Tang Q, Li W, Huang T, Huo X, et al. Sertoli cell-mediated differentiation of male germ cell-like cells from human umbilical cord Wharton’s jelly-derived mesenchymal stem cells in an in vitro co-culture system. Eur J Med Res 2015;20:9.
40. Mital P, Kaur G, Dufour JM. Immunoprotective sertoli cells: making allogeneic and xenogeneic transplantation feasible. Reproduction 2010;139:495-504.
41. Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm 2005;2:8-18.
42. Bibber B, Sinha G, Lobba ARM, Greco SJ, Rameshwar P. A review of stem cell translation and potential confounds by cancer stem cells. Stem Cells Int 2013;2013:Article ID 241048.
43. Aghamir SMK, Salavati A, Yousefie R, Tootian Z, Ghazaleh N, Jamali M, et al. Does bone marrow-derived mesenchymal stem cell transfusion prevent antisperm antibody production after traumatic testis rupture? Urology 2014;84:82-86.