Strategies for Mammalian Mesenchymal Stem Cells Differentiation into Primordial Germ Cell-Like Cells: A Review

Document Type : Review Article

Authors

1 Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Gynecologic Endocrinology and Fertility Disorders, Women's Hospital, Ruprecht-Karls University of Heidelberg, Heidelberg, Germany

3 Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

5 Student’s Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

6 Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Primordial germ cells develop into oocytes and sperm cells. These cells are useful resources in reproductive biology and regenerative medicine. The mesenchymal stem cells (MSCs) have been examined for in vitro production of primordial germ cell-like cells. This study aimed to summarize the existing protocols for MSCs differentiation into primordial germ cell-like cells (PGLCs). In the limited identified studies, various models of mesenchymal stem cells, including those derived from adipose tissue, bone marrow, and Wharton's jelly, have been successfully differentiated into primordial germ cell-like cells. Although the protocols of specification induction are basically very similar, they have been adjusted to the mesenchymal cell type and the species of origin. The availability of MSCs has made it possible to customize conditions for their differentiation into primordial germ cell-like cells in several models, including humans. Refining germ cell-related signaling pathways during induced differentiation of MSCs will help define extension to the protocols for primordial germ cell-like cells production.

Keywords


1. Kahnamouyi S, Nouri M, Farzadi L, Darabi M, Hosseini V, Mehdizadeh A. The role of mitogen-activated protein kinase–extracellular receptor kinase pathway in female fertility outcomes: a focus on pituitary gonadotropins regulation. Ther Adv Endocrinol Metab. 2018; 9(7): 209-215.
2. Chen D, Sun N, Hou L, Kim R, Faith J, Aslanyan M, et al. Human primordial germ cells are specified from lineage-primed progenitors. Cell Rep. 2019; 29(13): 4568-4582.
3. Larose H, Shami AN, Abbott H, Manske G, Lei L, Hammoud SS. Gametogenesis: a journey from inception to conception. Curr Top Dev Biol. 2019; 132: 257-310.
4. Suman S, Domingues A, Ratajczak J, Ratajczak MZ. Potential clinical applications of stem cells in regenerative medicine. Adv Exp Med Biol. 2019; 1201: 1-22.
5. Eguizabal C, Aran B, Chuva de Sousa Lopes SM, Geens M, Heindryckx B, Panula S, et al. Two decades of embryonic stem cells: a historical overview. Hum Reprod Open. 2019; 2019(1): hoy024.
6. Zhao YX, Chen SR, Su PP, Huang FH, Shi YC, Shi QY, et al. Using mesenchymal stem cells to treat female infertility: an update on female reproductive diseases. Stem Cells Int. 2019; 2019: 9071720.
7. Wuputra K, Ku CC, Wu DC, Lin YC, Saito S, Yokoyama KK. Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells. J Exp Clin Cancer Res. 2020; 39: 1-24.
8. 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.
9. Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther. 2019; 10(1): 1-22.
10. Mohr A, Zwacka R. The future of mesenchymal stem cell-based therapeutic approaches for cancer–From cells to ghosts. Cancer Lett. 2018; 414: 239-249.
11. Kumar K, Das K, Madhusoodan A, Kumar A, Singh P, Mondal T, et al. Rat bone marrow derived mesenchymal stem cells differentiate to germ cell like cells. Available from: biorxiv.org/ content/10.1101/418962v1.full (24 May 2021).
12. Lee SH. The advantages and limitations of mesenchymal stem cells in clinical application for treating human diseases. Osteoporos Sarcopenia. 2018; 4(4): 150.
13. Easley CA, Latov DR, Simerly CR, Schatten G. Adult somatic cells to the rescue: nuclear reprogramming and the dispensability of gonadal germ cells. Fertil Steril. 2014; 101(1): 14-19.
14. Sasaki K, Yokobayashi S, Nakamura T, Okamoto I, Yabuta Y, Kurimoto K, et al. Robust in vitro Induction of human germ cell fate from pluripotent stem cells. Cell Stem Cell. 2015; 17(2): 178-194.
15. Sun R, Sun YC, Ge W, Tan H, Cheng SF, Yin S, et al. The crucial role of Activin A on the formation of primordial germ cell-like cells from skin-derived stem cells in vitro. Cell Cycle. 2015; 14(19): 3016-3029.
16. García-Nieto PE, Morrison AJ, Fraser HB. The somatic mutation landscape of the human body. Genome Biol. 2019; 20(1): 1-20.
17. Rahbari R, Wuster A, Lindsay SJ, Hardwick RJ, Alexandrov LB, Turki SA, et al. Timing, rates and spectra of human germline mutation. Nat Genet. 2016; 48(2): 126-133.
18. Gell JJ, Liu W, Sosa E, Chialastri A, Hancock G, Tao Y, et al. An extended culture system that supports human primordial germ celllike cell survival and initiation of DNA methylation erasure. Stem Cell Rep. 2020; 14(3): 433-446.
19. Mitsunaga S, Shioda K, Isselbacher KJ, Hanna JH, Shioda T. Generation of human primordial germ cell-like cells at the surface of embryoid bodies from primed-pluripotency induced pluripotent stem cells. J Vis Exp. 2019; (143).
20. Gulimiheranmu M, Wang X, Zhou J. Advances in female germ cell induction from pluripotent stem cells. Stem Cells Int. 2021: 8849230.
21. Fang F, Li Z, Zhao Q, Ye Z, Gu X, Pan F, et al. Induced pluripotent stem cells derived from two idiopathic azoospermia patients display compromised differentiation potential for primordial germ cell fate. Front Cell Dev Biol. 2020; 8: 432.
22. Kojima Y, Sasaki K, Yokobayashi S, Sakai Y, Nakamura T, Yabuta Y, et al. Evolutionarily distinctive transcriptional and signaling programs drive human germ cell lineage specification from pluripotent stem cells. Cell Stem Cell. 2017; 21(4): 517-532.
23. Pierson Smela M, Sybirna A, Wong FCK, Surani MA. Testing the role of SOX15 in human primordial germ cell fate. Wellcome Open Res. 2019; 4: 122.
24. Yokobayashi S, Okita K, Nakagawa M, Nakamura T, Yabuta Y, Yamamoto T, et al. Clonal variation of human induced pluripotent stem cells for induction into the germ cell fate. Biol Reprod. 2017; 96(6): 1154-1166.
25. Shirzeily MH, Pasbakhsh P, Amidi F, Mehrannia K, Sobhani A. Comparison of differentiation potential of male mouse adipose tissue and bone marrow derived-mesenchymal stem cells into germ cells. Int J Reprod Biomed. 2013; 11(12): 965.
26. Saitou M, Miyauchi H. Gametogenesis from pluripotent stem cells. Cell Stem Cell. 2016; 18(6): 721-735.
27. Rassoulzadegan M, Cuzin F. Epigenetic heredity: RNA-mediated modes of phenotypic variation. Ann N Y Acad Sci. 2015; 1341: 172-175.
28. Zeng Y, Chen T. DNA methylation reprogramming during mammalian development. Genes. 2019; 10(4): 257.
29. Nicholls PK, Schorle H, Naqvi S, Hu YC, Fan Y, Carmell MA, et al. Mammalian germ cells are determined after PGC colonization of the nascent gonad. Proc Natl Acad Sci USA. 2019; 116(51): 25677-25687.
30. Wang JH, Li Y, Deng SL, Liu YX, Lian ZX, Yu K. Recent research advances in mitosis during mammalian gametogenesis. Cells. 2019; 8(6): 567.
31. 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(7): 654-663.
32. Shirazi R, Zarnani AH, Soleimani M, Abdolvahabi MA, Nayernia K, Kashani IR. BMP4 can generate primordial germ cells from bonemarrow- derived pluripotent stem cells. Cell Biol Int. 2012; 36(12): 1185-1193.
33. Mazaheri Z, Movahedin M, Rahbarizadeh F, Amanpour S. Different doses of bone morphogenetic protein 4 promote the expression of early germ cell-specific gene in bone marrow mesenchymal stem cells. In Vitro Cell Dev Biol Anim. 2011; 47(8): 521-525.
34. Ghasemzadeh-Hasankolaei M, Sedighi-Gilani M, Eslaminejad M. Induction of ram bone marrow mesenchymal stem cells into germ cell lineage using transforming growth factor-β superfamily growth factors. Reprod Domest Anim. 2014; 49(4): 588-598.
35. Asgari HR, Akbari M, Abbasi M, Ai J, Korouji M, Aliakbari F, et al. Human Wharton’s jelly-derived mesenchymal stem cells express oocyte developmental genes during co-culture with placental cells. Iran J Basic Med Sci. 2015; 18(1): 22.
36. Amidi F, Hoseini MA, Nia KN, Habibi M, Kajbafzadeh AM, Mazaheri Z, et al. Male germ-like cell differentiation potential of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells in coculture with human placenta cells in presence of BMP4 and retinoic acid. Iran J Basic Med Sci. 2015; 18(4): 325.
37. Dissanayake D, Patel H, Wijesinghe P. Differentiation of human male germ cells from Wharton’s jelly-derived mesenchymal stem cells. Clin Exp Reprod Med. 2018; 45(2): 75-81.
38. Li B, Liu W, Zhuang M, Li N, Wu S, Pan S, et al. Overexpression of CD61 promotes hUC-MSC differentiation into male germ-like cells. Cell Prolif. 2016; 49(1): 36-47.
39. Zolfaghar M, Mirzaeian L, Beiki B, Naji T, Moini A, Eftekhari-Yazdi P, et al. Wharton’s jelly derived mesenchymal stem cells differentiate into oocyte like cells in vitro by follicular fluid and cumulus cells conditioned medium. Heliyon. 2020; 6(10): e04992.
40. Alifi F, Asgari HR. Alteration in expression of primordial germ cell (PGC) markers during induction of human amniotic mesenchymal stem cells (hAMSCs). J Reprod Infertil. 2020; 21(1): 59.
41. Liu H, Chen M, Liu L, Ren S, Cheng P, Zhang H. Induction of human adipose-derived mesenchymal stem cells into germ lineage using retinoic acid. Cell Reprogram. 2018; 20(2): 127-134.
42. Bräunig P, Glanzner W, Rissi V, Gonçalves P. The differentiation potential of adipose tissue-derived mesenchymal stem cells into cell lineage related to male germ cells. Arq Bras Med Vet Zootec. 2018; 70(1): 160-168.
43. Luo Y, Xie L, Mohsin A, Ahmed W, Xu C, Peng Y, et al. Efficient generation of male germ-like cells derived during co-culturing of adipose-derived mesenchymal stem cells with Sertoli cells under retinoic acid and testosterone induction. Stem Cell Res Ther. 2019; 10(1): 91.
44. Mahboudi S, Parivar K, Mazaheri Z, Irani S. Mir-106b cluster regulates primordial germ cells differentiation from human mesenchymal stem cells. Cell J. 2021; 23(3): 294.
45. Fang J, Wei Y, Lv C, Peng S, Zhao S, Hua J. CD61 promotes the differentiation of canine ADMSCs into PGC-like cells through modulation of TGF-β signaling. Sci Rep. 2017; 7(1): 1-9.
46. Taheri M, Saki G, Nikbakht R, Eftekhari AR. Bone morphogenetic protein 15 induces differentiation of mesenchymal stem cells derived from human follicular fluid to oocyte-like cell. Cell Biol Int. 2021; 45(1): 127-139.
47. Li Q, Zhang S, Sui Y, Fu X, Li Y, Wei S. Sequential stimulation with different concentrations of BMP4 promotes the differentiation of human embryonic stem cells into dental epithelium with potential for tooth formation. Stem Cell Res Ther. 2019; 10(1): 1-8.
48. Toyooka Y, Tsunekawa N, Takahashi Y, Matsui Y, Satoh M, Noce T. Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mech Dev. 2000; 93(1-2): 139-149.
49. Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011; 9(1): 12.
50. Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev. 2011; 78(1): 9-21.
51. Han L, Monné M, Okumura H, Schwend T, Cherry AL, Flot D, et al. Insights into egg coat assembly and egg-sperm interaction from the X-ray structure of full-length ZP3. Cell. 2010; 143(3): 404-415.
52. Mongan NP, Gudas LJ. Diverse actions of retinoid receptors in cancer prevention and treatment. Differentiation. 2007; 75(9): 853-870.
53. Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science. 2007; 315(5813): 820-825.
54. Schug TT, Berry DC, Shaw NS, Travis SN, Noy N. Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors. Cell. 2007; 129(4): 723-733.
55. Gudas LJ, Wagner JA. Retinoids regulate stem cell differentiation. J Cell Physiol. 2011; 226(2): 322-330.
56. Li G, Margueron R, Hu G, Stokes D, Wang Y-H, Reinberg D. Highly compacted chromatin formed in vitro reflects the dynamics of transcription activation in vivo. Mol Cell. 2010; 38(1): 41-53.
57. Simon JA, Kingston RE. Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol. 2009; 10(10): 697-708.
58. Kashyap V, Gudas LJ. Epigenetic regulatory mechanisms distinguish retinoic acid-mediated transcriptional responses in stem cells and fibroblasts. J Biol Chem. 2010; 285(19): 14534-14548.
59. Amat R, Gudas LJ. RARγ is required for correct deposition and removal of Suz12 and H2A. Z in embryonic stem cells. J Cell Physiol. 2011; 226(2): 293-298.
60. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature. 2003; 425(6958): 577-584.
61. Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell. 2015; 160(1-2): 253-268.
62. Taylor RM. Investigation into germ cell fate determination of rat embryonic stem cells. Presented for the Ph.D., Edinburgh. University of Edinburgh. 2020.
63. Hayashi K, Surani MA. Self-renewing epiblast stem cells exhibit continual delineation of germ cells with epigenetic reprogramming in vitro. Development. 2009; 136(21): 3549-3556.
64. Oliveira GPMSda. The identification of novel factors required for the development of primordial germ cells. Presented for the Ph.D., Cambridge. University of Cambridge. 2020.
65. Fayezi S, Ghaffari Novin M, Darabi M, Norouzian M, Nouri M, Farzadi L. Primary culture of human cumulus cells requires stearoylcoenzyme A desaturase 1 activity for steroidogenesis and enhancing oocyte in vitro maturation. Reprod Sci. 2018; 25(6): 844-853.
66. Mardomi A, Nouri M, Farzadi L, Zarghami N, Mehdizadeh A, Yousefi M, et al. Human charcoal-stripped serum supplementation enhances both the stearoyl-coenzyme a desaturase 1 activity of cumulus cells and the. Hum Fertil (Camb). 2019; 22(3): 212-218.
67. Eyvaznejad E, Nouri M, Ghasemzadeh A, Mehdizadeh A, Shahnazi V, Asghari S, et al. Steroid-depleted polycystic ovarian syndrome serum promotes in vitro oocyte maturation and embryo development. Gynecol Endocrinol. 2018; 34(8): 698-703.
68. Yousefi S, Soleimanirad J, Hamdi K, Farzadi L, Ghasemzadeh A, Kazemi M, et al. Distinct effect of fetal bovine serum versus follicular fluid on multipotentiality of human granulosa cells in in vitro condition. Biologicals. 2018; 52: 44-48.