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Germ Line Stem Cells: A Promising Alternative Source for Stem-Cell-Based Therapies in Regenerative Medicine

Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Spermatogonial stem cells (SSCs) are exceptional cells with potential clinical applications in fertility preservation and regenerative medicine. Like other tissue-specific stem cells, SSCs are defined by their ability to balance between self-renewal and differentiation. This balance regulates the stem cell pool and guarantees the daily production of gametes. The preservation and transplantation of SSCs may become a promising strategy to treat reproductive stem cell loss disorders. As a consequence, the banking of testicular tissue from prepubertal patients is being introduced in a clinical setting. Moreover, with the increasing reports about the plasticity of mouse and human SSCs, their potential application in regenerative medicine is highly interesting. In contrast to males, females are born with a finite population of primordial follicles. Although the existence of ovarian stem cells (OSCs) has been suggested recently, it is still a matter of controversy. This review provides an update on the role of germ line stem cells in fertility restoration after germ cell loss, and gives an overview of (future) clinical applications making use of these fascinating cells.

Keywords

Sertoli Cell Seminiferous Tubule Testicular Tissue Primordial Follicle Spermatogonial Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We are very grateful for the financial support received from Methusalem, the Fund for Scientific Research-Flanders (FWO-Vlaanderen, Belgium), the Flemish League against Cancer, the Research Council of the Vrije Universiteit Brussel, and the Research Council of the UZ Brussel. E.G. is a Postdoctoral Fellow of the FWO-Vlaanderen.

References

  1. 1.
    Ying Y, Qi X, Zhao GQ (2001) Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways. Proc Natl Acad Sci U S A 98(14):7858–7862PubMedCrossRefGoogle Scholar
  2. 2.
    Fleischman RA (1993) From white spots to stem cells: the role of the Kit receptor in mammalian development. Trends Genet 9(8):285–290PubMedCrossRefGoogle Scholar
  3. 3.
    Vergouwen RP, Jacobs SG, Huiskamp R, Davids JA, de Rooij DG (1991) Proliferative activity of gonocytes, Sertoli cells and interstitial cells during testicular development in mice. J Reprod Fertil 93(1):233–243PubMedCrossRefGoogle Scholar
  4. 4.
    Ohta H, Wakayama T, Nishimune Y (2004) Commitment of fetal male germ cells to spermatogonial stem cells during mouse embryonic development. Biol Reprod 70(5):1286–1291PubMedCrossRefGoogle Scholar
  5. 5.
    Kubota H, Brinster RL (2006) Technology insight: In vitro culture of spermatogonial stem cells and their potential therapeutic uses. Nat Clin Pract Endocrinol Metab 2(2):99–108PubMedCrossRefGoogle Scholar
  6. 6.
    Shinohara T, Avarbock MR, Brinster RL (1999) beta1- and alpha6-integrin are surface markers on mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 96(10):5504–5509PubMedCrossRefGoogle Scholar
  7. 7.
    Meng X, Lindahl M, Hyvonen ME, Parvinen M, de Rooij DG, Hess MW, Raatikainen-Ahokas A, Sainio K, Rauvala H, Lakso M, Pichel JG, Westphal H, Saarma M, Sariola H (2000) Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 287(5457):1489–1493PubMedCrossRefGoogle Scholar
  8. 8.
    Giuili G, Tomljenovic A, Labrecque N, Oulad-Abdelghani M, Rassoulzadegan M, Cuzin F (2002) Murine spermatogonial stem cells: targeted transgene expression and purification in an active state. EMBO Rep 3(8):753–759PubMedCrossRefGoogle Scholar
  9. 9.
    Kubota H, Avarbock MR, Brinster RL (2003) Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci U S A 100(11):6487–6492PubMedCrossRefGoogle Scholar
  10. 10.
    Kanatsu-Shinohara M, Toyokuni S, Shinohara T (2004) CD9 is a surface marker on mouse and rat male germline stem cells. Biol Reprod 70(1):70–75PubMedCrossRefGoogle Scholar
  11. 11.
    Naughton CK, Jain S, Strickland AM, Gupta A, Milbrandt J (2006) Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Biol Reprod 74(2):314–321PubMedCrossRefGoogle Scholar
  12. 12.
    Izadyar F, Wong J, Maki C, Pacchiarotti J, Ramos T, Howerton K, Yuen C, Greilach S, Zhao HH, Chow M, Chow YC, Rao J, Barritt J, Bar-Chama N, Copperman A (2011) Identification and characterization of repopulating spermatogonial stem cells from the adult human testis. Hum Reprod 26(6):1296–1306PubMedCrossRefGoogle Scholar
  13. 13.
    Fujita K, Ohta H, Tsujimura A, Takao T, Miyagawa Y, Takada S, Matsumiya K, Wakayama T, Okuyama A (2005) Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia. J Clin Invest 115(7):1855–1861PubMedCrossRefGoogle Scholar
  14. 14.
    Yoshinaga K, Nishikawa S, Ogawa M, Hayashi S, Kunisada T, Fujimoto T (1991) Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. Development 113(2):689–699PubMedGoogle Scholar
  15. 15.
    Schnieders F, Dork T, Arnemann J, Vogel T, Werner M, Schmidtke J (1996) Testis-specific protein, Y-encoded (TSPY) expression in testicular tissues. Hum Mol Genet 5(11):1801–1807PubMedCrossRefGoogle Scholar
  16. 16.
    Kido T, Lau YF (2006) The rat Tspy is preferentially expressed in elongated spermatids and interacts with the core histones. Biochem Biophys Res Commun 350(1):56–67PubMedCrossRefGoogle Scholar
  17. 17.
    Aubry F, Satie AP, Rioux-Leclercq N, Rajpert-De Meyts E, Spagnoli GC, Chomez P, De Backer O, Jegou B, Samson M (2001) MAGE-A4, a germ cell specific marker, is expressed differentially in testicular tumors. Cancer 92(11):2778–2785PubMedCrossRefGoogle Scholar
  18. 18.
    Maki CB, Pacchiarotti J, Ramos T, Pascual M, Pham J, Kinjo J, Anorve S, Izadyar F (2009) Phenotypic and molecular characterization of spermatogonial stem cells in adult primate testes. Hum Reprod 24(6):1480–1491PubMedCrossRefGoogle Scholar
  19. 19.
    Nagano M, Brinster RL (1998) Spermatogonial transplantation and reconstitution of donor cell spermatogenesis in recipient mice. APMIS 106(1):47–55 (discussion 56–47)PubMedCrossRefGoogle Scholar
  20. 20.
    Yeh JR, Zhang X, Nagano MC (2007) Establishment of a short-term in vitro assay for mouse spermatogonial stem cells. Biol Reprod 77(5):897–904PubMedCrossRefGoogle Scholar
  21. 21.
    Ohmura M, Yoshida S, Ide Y, Nagamatsu G, Suda T, Ohbo K (2004) Spatial analysis of germ stem cell development in Oct-4/EGFP transgenic mice. Arch Histol Cytol 67(4):285–296PubMedCrossRefGoogle Scholar
  22. 22.
    Costoya JA, Hobbs RM, Barna M, Cattoretti G, Manova K, Sukhwani M, Orwig KE, Wolgemuth DJ, Pandolfi PP (2004) Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet 36(6):653–659PubMedCrossRefGoogle Scholar
  23. 23.
    Yoshida S, Takakura A, Ohbo K, Abe K, Wakabayashi J, Yamamoto M, Suda T, Nabeshima Y (2004) Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis. Dev Biol 269(2):447–458PubMedCrossRefGoogle Scholar
  24. 24.
    Raverot G, Weiss J, Park SY, Hurley L, Jameson JL (2005) Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis. Dev Biol 283(1):215–225PubMedCrossRefGoogle Scholar
  25. 25.
    Sada A, Suzuki A, Suzuki H, Saga Y (2009) The RNA-binding protein NANOS2 is required to maintain murine spermatogonial stem cells. Science 325(5946):1394–1398PubMedCrossRefGoogle Scholar
  26. 26.
    Nakagawa T, Sharma M, Nabeshima Y, Braun RE, Yoshida S (2011) Functional hierarchy and reversibility within the murine spermatogenic stem cell compartment. Science 328(5974):62–67CrossRefGoogle Scholar
  27. 27.
    Zheng K, Wu X, Kaestner KH, Wang PJ (2009) The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse. BMC Dev Biol 9:38PubMedCrossRefGoogle Scholar
  28. 28.
    Grisanti L, Falciatori I, Grasso M, Dovere L, Fera S, Muciaccia B, Fuso A, Berno V, Boitani C, Stefanini M, Vicini E (2009) Identification of spermatogonial stem cell subsets by morphological analysis and prospective isolation. Stem Cells 27(12):3043–3052PubMedGoogle Scholar
  29. 29.
    Suzuki H, Sada A, Yoshida S, Saga Y (2009) The heterogeneity of spermatogonia is revealed by their topology and expression of marker proteins including the germ cell-specific proteins NANOS2 and NANOS3. Dev Biol 336(2):222–231PubMedCrossRefGoogle Scholar
  30. 30.
    Oatley MJ, Kaucher AV, Racicot KE, Oatley JM (2011) Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice. Biol Reprod 85(2):347–356PubMedCrossRefGoogle Scholar
  31. 31.
    Phillips BT, Gassei K, Orwig KE (2011) Spermatogonial stem cell regulation and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 365(1546):1663–1678Google Scholar
  32. 32.
    Tran J, Brenner TJ, DiNardo S (2000) Somatic control over the germline stem cell lineage during Drosophila spermatogenesis. Nature 407(6805):754–757PubMedCrossRefGoogle Scholar
  33. 33.
    Ogawa T, Ohmura M, Ohbo K (2005) The niche for spermatogonial stem cells in the mammalian testis. Int J Hematol 82(5):381–388PubMedCrossRefGoogle Scholar
  34. 34.
    Cheng CY, Mruk DD (2002) Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiol Rev 82(4):825–874PubMedGoogle Scholar
  35. 35.
    Oatley JM, Oatley MJ, Avarbock MR, Tobias JW, Brinster RL (2009) Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 136(7):1191–1199PubMedCrossRefGoogle Scholar
  36. 36.
    Yoshida S, Sukeno M, Nabeshima Y (2007) A vasculature-associated niche for undifferentiated spermatogonia in the mouse testis. Science 317(5845):1722–1726PubMedCrossRefGoogle Scholar
  37. 37.
    Wu X, Schmidt JA, Avarbock MR, Tobias JW, Carlson CA, Kolon TF, Ginsberg JP, Brinster RL (2009) Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc Natl Acad Sci U S A 106(51):21672–21677PubMedCrossRefGoogle Scholar
  38. 38.
    van Beek ME, Meistrich ML, de Rooij DG (1990) Probability of self-renewing divisions of spermatogonial stem cells in colonies, formed after fission neutron irradiation. Cell Tissue Kinet 23(1):1–16PubMedGoogle Scholar
  39. 39.
    Oakberg EF (1971) Spermatogonial stem-cell renewal in the mouse. Anat Rec 169(3):515–531PubMedCrossRefGoogle Scholar
  40. 40.
    Huckins C (1971) The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat Rec 169(3):533–557PubMedCrossRefGoogle Scholar
  41. 41.
    Ohbo K, Yoshida S, Ohmura M, Ohneda O, Ogawa T, Tsuchiya H, Kuwana T, Kehler J, Abe K, Scholer HR, Suda T (2003) Identification and characterization of stem cells in prepubertal spermatogenesis in mice small star, filled. Dev Biol 258(1):209–225PubMedCrossRefGoogle Scholar
  42. 42.
    Barroca V, Lassalle B, Coureuil M, Louis JP, Le Page F, Testart J, Allemand I, Riou L, Fouchet P (2009) Mouse differentiating spermatogonia can generate germinal stem cells in vivo. Nat Cell Biol 11(2):190–196PubMedCrossRefGoogle Scholar
  43. 43.
    Clermont Y (1966) Renewal of spermatogonia in man. Am J Anat 118(2):509–524PubMedCrossRefGoogle Scholar
  44. 44.
    van Alphen MM, van de Kant HJ, de Rooij DG (1988) Depletion of the spermatogonia from the seminiferous epithelium of the rhesus monkey after X irradiation. Radiat Res 113(3):473–486PubMedCrossRefGoogle Scholar
  45. 45.
    Ehmcke J, Simorangkir DR, Schlatt S (2005) Identification of the starting point for spermatogenesis and characterization of the testicular stem cell in adult male rhesus monkeys. Hum Reprod 20(5):1185–1193PubMedCrossRefGoogle Scholar
  46. 46.
    Nagano M, Avarbock MR, Leonida EB, Brinster CJ, Brinster RL (1998) Culture of mouse spermatogonial stem cells. Tissue Cell 30(4):389–397PubMedCrossRefGoogle Scholar
  47. 47.
    Nagano M, Shinohara T, Avarbock MR, Brinster RL (2000) Retrovirus-mediated gene delivery into male germ line stem cells. FEBS Lett 475(1):7–10PubMedCrossRefGoogle Scholar
  48. 48.
    Nagano M, Ryu BY, Brinster CJ, Avarbock MR, Brinster RL (2003) Maintenance of mouse male germ line stem cells in vitro. Biol Reprod 68(6):2207–2214PubMedCrossRefGoogle Scholar
  49. 49.
    Kanatsu-Shinohara M, Ogonuki N, Inoue K, Miki H, Ogura A, Toyokuni S, Shinohara T (2003) Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol Reprod 69(2):612–616PubMedCrossRefGoogle Scholar
  50. 50.
    Kanatsu-Shinohara M, Shinohara T (2007) Culture and genetic modification of mouse germline stem cells. Ann N Y Acad Sci 1120:59–71PubMedCrossRefGoogle Scholar
  51. 51.
    Kanatsu-Shinohara M, Ogonuki N, Iwano T, Lee J, Kazuki Y, Inoue K, Miki H, Takehashi M, Toyokuni S, Shinkai Y, Oshimura M, Ishino F, Ogura A, Shinohara T (2005) Genetic and epigenetic properties of mouse male germline stem cells during long-term culture. Development 132(18):4155–4163PubMedCrossRefGoogle Scholar
  52. 52.
    Kanatsu-Shinohara M, Inoue K, Ogonuki N, Morimoto H, Ogura A, Shinohara T (2011) Serum- and feeder-free culture of mouse germline stem cells. Biol Reprod 84(1):97–105PubMedCrossRefGoogle Scholar
  53. 53.
    Aponte PM, Soda T, Teerds KJ, Mizrak SC, van de Kant HJ, de Rooij DG (2008) Propagation of bovine spermatogonial stem cells in vitro. Reproduction 136(5):543–557PubMedCrossRefGoogle Scholar
  54. 54.
    Sadri-Ardekani H, Akhondi MA, van der Veen F, Repping S, van Pelt AM (2011) In vitro propagation of human prepubertal spermatogonial stem cells. JAMA 305(23):2416–2418PubMedCrossRefGoogle Scholar
  55. 55.
    Sadri-Ardekani H, Mizrak SC, van Daalen SK, Korver CM, Roepers-Gajadien HL, Koruji M, Hovingh S, de Reijke TM, de la Rosette JJ, van der Veen F, de Rooij DG, Repping S, van Pelt AM (2009) Propagation of human spermatogonial stem cells in vitro. JAMA 302(19):2127–2134PubMedCrossRefGoogle Scholar
  56. 56.
    Stukenborg JB, Schlatt S, Simoni M, Yeung CH, Elhija MA, Luetjens CM, Huleihel M, Wistuba J (2009) New horizons for in vitro spermatogenesis? An update on novel three-dimensional culture systems as tools for meiotic and post-meiotic differentiation of testicular germ cells. Mol Hum Reprod 15(9):521–529PubMedCrossRefGoogle Scholar
  57. 57.
    Izadyar F, Spierenberg GT, Creemers LB, den Ouden K, de Rooij DG (2002) Isolation and purification of type A spermatogonia from the bovine testis. Reproduction 124(1):85–94PubMedCrossRefGoogle Scholar
  58. 58.
    Oatley JM, de Avila DM, Reeves JJ, McLean DJ (2004) Testis tissue explant culture supports survival and proliferation of bovine spermatogonial stem cells. Biol Reprod 70(3):625–631PubMedCrossRefGoogle Scholar
  59. 59.
    Sato T, Katagiri K, Gohbara A, Inoue K, Ogonuki N, Ogura A, Kubota Y, Ogawa T (2011) In vitro production of functional sperm in cultured neonatal mouse testes. Nature 471(7339):504–507PubMedCrossRefGoogle Scholar
  60. 60.
    Howell SJ, Shalet SM (2005) Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr 34:12–17PubMedCrossRefGoogle Scholar
  61. 61.
    Aksglaede L, Wikstrom AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A (2006) Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update 12(1):39–48PubMedCrossRefGoogle Scholar
  62. 62.
    Tournaye H, Goossens E, Verheyen G, Frederickx V, De Block G, Devroey P, Van Steirteghem A (2004) Preserving the reproductive potential of men and boys with cancer: current concepts and future prospects. Hum Reprod Update 10(6):525–532PubMedCrossRefGoogle Scholar
  63. 63.
    Schlatt S (2002) Spermatogonial stem cell preservation and transplantation. Mol Cell Endocrinol 187(1–2):107–111PubMedCrossRefGoogle Scholar
  64. 64.
    Milazzo JP, Vaudreuil L, Cauliez B, Gruel E, Masse L, Mousset-Simeon N, Mace B, Rives N (2008) Comparison of conditions for cryopreservation of testicular tissue from immature mice. Hum Reprod 23(1):17–28PubMedCrossRefGoogle Scholar
  65. 65.
    Shinohara T, Inoue K, Ogonuki N, Kanatsu-Shinohara M, Miki H, Nakata K, Kurome M, Nagashima H, Toyokuni S, Kogishi K, Honjo T, Ogura A (2002) Birth of offspring following transplantation of cryopreserved immature testicular pieces and in vitro micro insemination. Hum Reprod 17(12):3039–3045PubMedCrossRefGoogle Scholar
  66. 66.
    Kvist K, Thorup J, Byskov AG, Hoyer PE, Mollgard K, Yding Andersen C (2006) Cryopreservation of intact testicular tissue from boys with cryptorchidism. Hum Reprod 21(2):484–491PubMedCrossRefGoogle Scholar
  67. 67.
    Keros V, Hultenby K, Borgstrom B, Fridstrom M, Jahnukainen K, Hovatta O (2007) Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Hum Reprod 22(5):1384–1395PubMedCrossRefGoogle Scholar
  68. 68.
    Jahnukainen K, Ehmcke J, Hergenrother SD, Schlatt S (2007) Effect of cold storage and cryopreservation of immature non-human primate testicular tissue on spermatogonial stem cell potential in xenografts. Hum Reprod 22(4):1060–1067PubMedCrossRefGoogle Scholar
  69. 69.
    Ohta H, Sakaide Y, Wakayama T (2008) The birth of mice from testicular spermatozoa retrieved from frozen testicular sections. Biol Reprod 78(5):807–811PubMedCrossRefGoogle Scholar
  70. 70.
    Honaramooz A, Megee SO, Dobrinski I (2002) Germ cell transplantation in pigs. Biol Reprod 66(1):21–28PubMedCrossRefGoogle Scholar
  71. 71.
    Zeng W, Snedaker AK, Megee S, Rathi R, Chen F, Honaramooz A, Dobrinski I (2009) Preservation and transplantation of porcine testis tissue. Reprod Fertil Dev 21(3):489–497PubMedCrossRefGoogle Scholar
  72. 72.
    Abrishami M, Anzar M, Yang Y, Honaramooz A (2010) Cryopreservation of immature porcine testis tissue to maintain its developmental potential after xenografting into recipient mice. Theriogenology 73(1):86–96PubMedCrossRefGoogle Scholar
  73. 73.
    Curaba M, Verleysen M, Amorim CA, Dolmans MM, Van Langendonckt A, Hovatta O, Wyns C, Donnez J (2011) Cryopreservation of prepubertal mouse testicular tissue by vitrification. Fertil Steril 95(4):1229–1234 e1221PubMedCrossRefGoogle Scholar
  74. 74.
    Curaba M, Poels J, van Langendonckt A, Donnez J, Wyns C (2011) Can prepubertal human testicular tissue be cryopreserved by vitrification? Fertil Steril 95(6):2123 e2129–2112Google Scholar
  75. 75.
    Brinster RL, Avarbock MR (1994) Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci U S A 91(24):11303–11307PubMedCrossRefGoogle Scholar
  76. 76.
    Avarbock MR, Brinster CJ, Brinster RL (1996) Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat Med 2(6):693–696PubMedCrossRefGoogle Scholar
  77. 77.
    Honaramooz A, Behboodi E, Blash S, Megee SO, Dobrinski I (2003) Germ cell transplantation in goats. Mol Reprod Dev 64(4):422–428PubMedCrossRefGoogle Scholar
  78. 78.
    Kim Y, Turner D, Nelson J, Dobrinski I, McEntee M, Travis AJ (2008) Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog. Reproduction 136(6):823–831PubMedCrossRefGoogle Scholar
  79. 79.
    Schlatt S, Rosiepen G, Weinbauer GF, Rolf C, Brook PF, Nieschlag E (1999) Germ cell transfer into rat, bovine, monkey and human testes. Hum Reprod 14(1):144–150PubMedCrossRefGoogle Scholar
  80. 80.
    Dobrinski I, Avarbock MR, Brinster RL (1999) Transplantation of germ cells from rabbits and dogs into mouse testes. Biol Reprod 61(5):1331–1339PubMedCrossRefGoogle Scholar
  81. 81.
    Ogawa T, Dobrinski I, Avarbock MR, Brinster RL (1999) Xenogeneic spermatogenesis following transplantation of hamster germ cells to mouse testes. Biol Reprod 60(2):515–521PubMedCrossRefGoogle Scholar
  82. 82.
    Goossens E, Frederickx V, De Block G, Van Steirteghem AC, Tournaye H (2003) Reproductive capacity of sperm obtained after germ cell transplantation in a mouse model. Hum Reprod 18(9):1874–1880PubMedCrossRefGoogle Scholar
  83. 83.
    Goossens E, De Block G, Tournaye H (2008) Computer-assisted motility analysis of spermatozoa obtained after spermatogonial stem cell transplantation in the mouse. Fertil Steril 90(4 Suppl):1411–1416PubMedCrossRefGoogle Scholar
  84. 84.
    Goossens E, De Rycke M, Haentjens P, Tournaye H (2009) DNA methylation patterns of spermatozoa and two generations of offspring obtained after murine spermatogonial stem cell transplantation. Hum Reprod 24(9):2255–2263PubMedCrossRefGoogle Scholar
  85. 85.
    Goossens E, de Vos P, Tournaye H (2010) Array comparative genomic hybridization analysis does not show genetic alterations in spermatozoa and offspring generated after spermatogonial stem cell transplantation in the mouse. Hum Reprod 25(7):1836–1842PubMedCrossRefGoogle Scholar
  86. 86.
    Jahnukainen K, Hou M, Petersen C, Setchell B, Soder O (2001) Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. Cancer Res 61(2):706–710PubMedGoogle Scholar
  87. 87.
    Geens M, Van de Velde H, De Block G, Goossens E, Van Steirteghem A, Tournaye H (2007) The efficiency of magnetic-activated cell sorting and fluorescence-activated cell sorting in the decontamination of testicular cell suspensions in cancer patients. Hum Reprod 22(3):733–742PubMedCrossRefGoogle Scholar
  88. 88.
    Fujita K, Tsujimura A, Miyagawa Y, Kiuchi H, Matsuoka Y, Takao T, Takada S, Nonomura N, Okuyama A (2006) Isolation of germ cells from leukemia and lymphoma cells in a human in vitro model: potential clinical application for restoring human fertility after anticancer therapy. Cancer Res 66(23):11166–11171PubMedCrossRefGoogle Scholar
  89. 89.
    Geens M, Goossens E, Tournaye H (2011) Cell selection by selective matrix adhesion is not sufficiently efficient for complete malignant cell depletion from contaminated human testicular cell suspensions. Fertil Steril 95(2):787–791PubMedCrossRefGoogle Scholar
  90. 90.
    Honaramooz A, Snedaker A, Boiani M, Scholer H, Dobrinski I, Schlatt S (2002) Sperm from neonatal mammalian testes grafted in mice. Nature 418(6899):778–781PubMedCrossRefGoogle Scholar
  91. 91.
    Schlatt S, Honaramooz A, Boiani M, Scholer HR, Dobrinski I (2003) Progeny from sperm obtained after ectopic grafting of neonatal mouse testes. Biol Reprod 68(6):2331–2335PubMedCrossRefGoogle Scholar
  92. 92.
    Schlatt S, Kim SS, Gosden R (2002) Spermatogenesis and steroidogenesis in mouse, hamster and monkey testicular tissue after cryopreservation and heterotopic grafting to castrated hosts. Reproduction 124(3):339–346PubMedCrossRefGoogle Scholar
  93. 93.
    Honaramooz A, Li MW, Penedo MC, Meyers S, Dobrinski I (2004) Accelerated maturation of primate testis by xenografting into mice. Biol Reprod 70(5):1500–1503PubMedCrossRefGoogle Scholar
  94. 94.
    Oatley JM, de Avila DM, Reeves JJ, McLean DJ (2004) Spermatogenesis and germ cell transgene expression in xenografted bovine testicular tissue. Biol Reprod 71(2):494–501PubMedCrossRefGoogle Scholar
  95. 95.
    Schlatt S, Honaramooz A, Ehmcke J, Goebell PJ, Rubben H, Dhir R, Dobrinski I, Patrizio P (2006) Limited survival of adult human testicular tissue as ectopic xenograft. Hum Reprod 21(2):384–389PubMedCrossRefGoogle Scholar
  96. 96.
    Geens M, De Block G, Goossens E, Frederickx V, Van Steirteghem A, Tournaye H (2006) Spermatogonial survival after grafting human testicular tissue to immunodeficient mice. Hum Reprod 21(2):390–396PubMedCrossRefGoogle Scholar
  97. 97.
    Wyns C, Van Langendonckt A, Wese FX, Donnez J, Curaba M (2008) Long-term spermatogonial survival in cryopreserved and xenografted immature human testicular tissue. Hum Reprod 23(11):2402–2414PubMedCrossRefGoogle Scholar
  98. 98.
    Van Saen D, Goossens E, Bourgain C, Ferster A, Tournaye H (2011) Meiotic activity in orthotopic xenografts derived from human postpubertal testicular tissue. Hum Reprod 26(2):282–293PubMedCrossRefGoogle Scholar
  99. 99.
    Van Saen D, Goossens E, De Block G, Tournaye H (2009) Regeneration of spermatogenesis by grafting testicular tissue or injecting testicular cells into the testes of sterile mice: a comparative study. Fertil Steril 91(5 Suppl):2264–2272PubMedCrossRefGoogle Scholar
  100. 100.
    Goossens E, Bilgec T, Van Saen D, Tournaye H (2011) Mouse germ cells go through typical epigenetic modifications after intratesticular tissue grafting. Hum Reprod (2011)Google Scholar
  101. 101.
    Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T (2004) Generation of pluripotent stem cells from neonatal mouse testis. Cell 119(7):1001–1012PubMedCrossRefGoogle Scholar
  102. 102.
    Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G (2006) Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 440(7088):1199–1203PubMedCrossRefGoogle Scholar
  103. 103.
    Izadyar F, Pau F, Marh J, Slepko N, Wang T, Gonzalez R, Ramos T, Howerton K, Sayre C, Silva F (2008) Generation of multipotent cell lines from a distinct population of male germ line stem cells. Reproduction 135(6):771–784PubMedCrossRefGoogle Scholar
  104. 104.
    Conrad S, Renninger M, Hennenlotter J, Wiesner T, Just L, Bonin M, Aicher W, Buhring HJ, Mattheus U, Mack A, Wagner HJ, Minger S, Matzkies M, Reppel M, Hescheler J, Sievert KD, Stenzl A, Skutella T (2008) Generation of pluripotent stem cells from adult human testis. Nature 456(7220):344–349PubMedCrossRefGoogle Scholar
  105. 105.
    Kossack N, Meneses J, Shefi S, Nguyen HN, Chavez S, Nicholas C, Gromoll J, Turek PJ, Reijo-Pera RA (2009) Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells 27(1):138–149PubMedCrossRefGoogle Scholar
  106. 106.
    Seandel M, James D, Shmelkov SV, Falciatori I, Kim J, Chavala S, Scherr DS, Zhang F, Torres R, Gale NW, Yancopoulos GD, Murphy A, Valenzuela DM, Hobbs RM, Pandolfi PP, Rafii S (2007) Generation of functional multipotent adult stem cells from GPR125 + germline progenitors. Nature 449(7160):346–350PubMedCrossRefGoogle Scholar
  107. 107.
    Ko K, Arauzo-Bravo MJ, Tapia N, Kim J, Lin Q, Bernemann C, Han DW, Gentile L, Reinhardt P, Greber B, Schneider RK, Kliesch S, Zenke M, Scholer HR (2010) Human adult germline stem cells in question. Nature 465(7301): E1 (discussion E3)Google Scholar
  108. 108.
    Geijsen N, Hochedlinger K (2009) gPS navigates germ cells to pluripotency. Cell Stem Cell 5(1):3–4PubMedCrossRefGoogle Scholar
  109. 109.
    Glaser T, Opitz T, Kischlat T, Konang R, Sasse P, Fleischmann BK, Engel W, Nayernia K, Brustle O (2008) Adult germ line stem cells as a source of functional neurons and glia. Stem Cells 26(9):2434–2443PubMedCrossRefGoogle Scholar
  110. 110.
    Streckfuss-Bomeke K, Vlasov A, Hulsmann S, Yin D, Nayernia K, Engel W, Hasenfuss G, Guan K (2009) Generation of functional neurons and glia from multipotent adult mouse germ-line stem cells. Stem Cell Res 2(2):139–154PubMedCrossRefGoogle Scholar
  111. 111.
    Guan K, Wagner S, Unsold B, Maier LS, Kaiser D, Hemmerlein B, Nayernia K, Engel W, Hasenfuss G (2007) Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells. Circ Res 100(11):1615–1625PubMedCrossRefGoogle Scholar
  112. 112.
    Simon L, Ekman GC, Kostereva N, Zhang Z, Hess RA, Hofmann MC, Cooke PS (2009) Direct trans differentiation of stem/progenitor spermatogonia into reproductive and nonreproductive tissues of all germ layers. Stem Cells 27(7):1666–1675PubMedCrossRefGoogle Scholar
  113. 113.
    Ning L, Goossens E, Geens M, Van Saen D, Van Riet I, He D, Tournaye H (2010) Mouse spermatogonial stem cells obtain morphologic and functional characteristics of hematopoietic cells in vivo. Hum Reprod 25(12):3101–3109PubMedCrossRefGoogle Scholar
  114. 114.
    Baeyens L, Bouwens L (2008) Can beta-cells be derived from exocrine pancreas? Diabetes Obes Metab 10(Suppl 4):170–178PubMedCrossRefGoogle Scholar
  115. 115.
    Eberhard D, Tosh D (2008) Trans differentiation and metaplasia as a paradigm for understanding development and disease. Cell Mol Life Sci 65(1):33–40PubMedCrossRefGoogle Scholar
  116. 116.
    Kanatsu-Shinohara M, Shinohara T (2006) The germ of pluripotency. Nat Biotechnol 24(6):663–664PubMedCrossRefGoogle Scholar
  117. 117.
    Kanatsu-Shinohara M, Toyokuni S, Shinohara T (2004) Transgenic mice produced by retroviral transduction of male germ line stem cells in vivo. Biol Reprod 71(4):1202–1207PubMedCrossRefGoogle Scholar
  118. 118.
    de Sousa Lopes SM, Hayashi K, Surani MA (2007) Proximal visceral endoderm and extraembryonic ectoderm regulate the formation of primordial germ cell precursors. BMC Dev Biol 7:140Google Scholar
  119. 119.
    Eppig JJ (2001) Oocyte control of ovarian follicular development and function in mammals. Reproduction 122(6):829–838PubMedCrossRefGoogle Scholar
  120. 120.
    Edson MA, Nagaraja AK, Matzuk MM (2009) The mammalian ovary from genesis to revelation. Endocr Rev 30(6):624–712PubMedCrossRefGoogle Scholar
  121. 121.
    Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428(6979):145–150PubMedCrossRefGoogle Scholar
  122. 122.
    Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL (2005) Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 122(2):303–315PubMedCrossRefGoogle Scholar
  123. 123.
    Lee HJ, Selesniemi K, Niikura Y, Niikura T, Klein R, Dombkowski DM, Tilly JL (2007) Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure. J Clin Oncol 25(22):3198–3204PubMedCrossRefGoogle Scholar
  124. 124.
    Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ (2006) Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature 441(7097):1109–1114PubMedCrossRefGoogle Scholar
  125. 125.
    Fu X, He Y, Xie C, Liu W (2008) Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage. Cytotherapy 10(4):353–363PubMedCrossRefGoogle Scholar
  126. 126.
    De Felici M (2010) Germ stem cells in the mammalian adult ovary: considerations by a fan of the primordial germ cells. Mol Hum Reprod 16(9):632–636PubMedCrossRefGoogle Scholar
  127. 127.
    Okamoto S, Okamoto A, Nikaido T, Saito M, Takao M, Yanaihara N, Takakura S, Ochiai K, Tanaka T (2009) Mesenchymal to epithelial transition in the human ovarian surface epithelium focusing on inclusion cysts. Oncol Rep 21(5):1209–1214PubMedCrossRefGoogle Scholar
  128. 128.
    Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB (2004) Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod Biol Endocrinol 2:20PubMedCrossRefGoogle Scholar
  129. 129.
    Bukovsky A, Svetlikova M, Caudle MR (2005) Oogenesis in cultures derived from adult human ovaries. Reprod Biol Endocrinol 3:17PubMedCrossRefGoogle Scholar
  130. 130.
    Zou K, Yuan Z, Yang Z, Luo H, Sun K, Zhou L, Xiang J, Shi L, Yu Q, Zhang Y, Hou R, Wu J (2009) Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol 11(5):631–636PubMedCrossRefGoogle Scholar
  131. 131.
    Begum S, Papaioannou VE, Gosden RG (2008) The oocyte population is not renewed in transplanted or irradiated adult ovaries. Hum Reprod 23(10):2326–2330PubMedCrossRefGoogle Scholar
  132. 132.
    Donnez J, Silber S, Andersen CY, Demeestere I, Piver P, Meirow D, Pellicer A, Dolmans MM (2011) Children born after autotransplantation of cryopreserved ovarian tissue. a review of 13 live births. Ann Med 43(6):437–450PubMedCrossRefGoogle Scholar
  133. 133.
    Kim SS, Lee WS, Chung MK, Lee HC, Lee HH, Hill D (2009) Long-term ovarian function and fertility after heterotopic autotransplantation of cryobanked human ovarian tissue: 8 year experience in cancer patients. Fertil Steril 91(6):2349–2354PubMedCrossRefGoogle Scholar
  134. 134.
    Oktay K, Buyuk E, Veeck L, Zaninovic N, Xu K, Takeuchi T, Opsahl M, Rosenwaks Z (2004) Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet 363(9412):837–840PubMedCrossRefGoogle Scholar
  135. 135.
    Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, Picton HM, Plancha C, Shea LD, Stouffer RL, Telfer EE, Woodruff TK, Zelinski MB (2010) Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation. Hum Reprod Update 16(4):395–414PubMedCrossRefGoogle Scholar
  136. 136.
    Abir R, Nitke S, Ben-Haroush A, Fisch B (2006) In vitro maturation of human primordial ovarian follicles: clinical significance, progress in mammals, and methods for growth evaluation. Histol Histopathol 21(8):887–898PubMedGoogle Scholar
  137. 137.
    Xu M, Kreeger PK, Shea LD, Woodruff TK (2006) Tissue-engineered follicles produce live, fertile offspring. Tissue Eng 12(10):2739–2746PubMedCrossRefGoogle Scholar
  138. 138.
    Hutt KJ, Albertini DF (2006) Clinical applications and limitations of current ovarian stem cell research: a review. J Exp Clin Assist Reprod 3:6PubMedCrossRefGoogle Scholar
  139. 139.
    Dym M, Kokkinaki M, He Z (2009) Spermatogonial stem cells: mouse and human comparisons. Birth Defects Res C Embryo Today 87(1), 27-34PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Biology of the Testis (BITE)Vrije Universiteit BrusselBrusselsBelgium
  2. 2.Centre for Reproductive MedicineUZ BrusselBrusselsBelgium

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