Semin Reprod Med 2013; 31(01): 039-048
DOI: 10.1055/s-0032-1331796
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Adult Stem Cells in the Human Testis

Ellen Goossens
1   Biology of the Testis (BITE), Vrije Universiteit Brussel
,
Herman Tournaye
2   Centre for Reproductive Medicine, Laarbeeklaan, Brussels, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
17 January 2013 (online)

Abstract

The primary function of the mammalian testis is the production of both gametes and hormones over a reproductive lifespan. This production of gametes proceeds in the seminiferous tubules and is supported by a stem cell population, the spermatogonial stem cells (SSCs). Like other tissue-specific stem cells, SSCs are defined by their ability to balance between self-renewal and differentiation. This balance maintains the stem cell pool and guarantees the daily production of spermatozoa from puberty onward. Studying SSCs is difficult because they are very few in number (0.03% of all germ cells), and specific markers have not been identified so far. Most of our knowledge results from experiments in rodent models. Very little is known about human SSCs. This review provides an update on SSCs, on their role in male fertility, and on (future) clinical applications using these fascinating cells.

 
  • References

  • 1 Lawson KA, Dunn NR, Roelen BA , et al. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 1999; 13 (4) 424-436
  • 2 Ying Y, Qi X, Zhao GQ. Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways. Proc Natl Acad Sci U S A 2001; 98 (14) 7858-7862
  • 3 Ginsburg M, Snow MH, McLaren A. Primordial germ cells in the mouse embryo during gastrulation. Development 1990; 110 (2) 521-528
  • 4 Fleischman RA. From white spots to stem cells: the role of the Kit receptor in mammalian development. Trends Genet 1993; 9 (8) 285-290
  • 5 Bendel-Stenzel M, Anderson R, Heasman J, Wylie C. The origin and migration of primordial germ cells in the mouse. Semin Cell Dev Biol 1998; 9 (4) 393-400
  • 6 Sapsford CS. Changes in the cells of the sex cords and the seminiferous tubules during development of the testis of the rat and the mouse. Aust J Zool 1962; 10: 178-192
  • 7 Tam PP, Snow MHL. Proliferation and migration of primordial germ cells during compensatory growth in mouse embryos. J Embryol Exp Morphol 1981; 64: 133-147
  • 8 McLaren A. Primordial germ cells in the mouse. Dev Biol 2003; 262 (1) 1-15
  • 9 Töhönen V, Ritzén EM, Nordqvist K, Wedell A. Male sex determination and prenatal differentiation of the testis. Endocr Dev 2003; 5: 1-23
  • 10 Huckins C, Clermont Y. Evolution of gonocytes in the rat testis during late embryonic and early post-natal life. Arch Anat Histol Embryol 1968; 51 (1) 341-354
  • 11 Vergouwen RPFA, Jacobs SGPM, Huiskamp R, Davids JAG, de Rooij DG. Proliferative activity of interstitial cells, Sertoli cells and gonocytes during testicular development in the mouse. J Reprod Fertil 1991; 93: 233-243
  • 12 Huckins C. The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat Rec 1971; 169 (3) 533-557
  • 13 Oakberg EF. Spermatogonial stem-cell renewal in the mouse. Anat Rec 1971; 169 (3) 515-531
  • 14 de Rooij DG, Russell LD. All you wanted to know about spermatogonia but were afraid to ask. J Androl 2000; 21 (6) 776-798
  • 15 Suzuki H, Sada A, Yoshida S, Saga Y. 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 2009; 336 (2) 222-231
  • 16 Zheng K, Wu X, Kaestner KH, Wang PJ. The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse. BMC Dev Biol 2009; 9: 38
  • 17 Oatley MJ, Kaucher AV, Racicot KE, Oatley JM. 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 2011; 85 (2) 347-356
  • 18 Brinster RL, Zimmermann JW. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci U S A 1994; 91 (24) 11298-11302
  • 19 Brinster RL, Avarbock MR. Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci U S A 1994; 91 (24) 11303-11307
  • 20 Shinohara T, Orwig KE, Avarbock MR, Brinster RL. Spermatogonial stem cell enrichment by multiparameter selection of mouse testis cells. Proc Natl Acad Sci U S A 2000; 97 (15) 8346-8351
  • 21 Ohbo K, Yoshida S, Ohmura M , et al. Identification and characterization of stem cells in prepubertal spermatogenesis in mice small star, filled. Dev Biol 2003; 258 (1) 209-225
  • 22 Barroca V, Lassalle B, Coureuil M , et al. Mouse differentiating spermatogonia can generate germinal stem cells in vivo. Nat Cell Biol 2009; 11 (2) 190-196
  • 23 Clermont Y, Hermo L. Spermatogonial stem cells and their behavior in the seminiferous epithelium of rats and monkeys. In: Cairnie AB, Lala PK, Osmond DG, , eds. Stem Cells of Renewing Cell Populations. New York, NY: Academic Press; 1976: 273-286
  • 24 van Alphen MMA, van de Kant HJG, de Rooij DG. Depletion of the spermatogonia from the seminiferous epithelium of the rhesus monkey after X irradiation. Radiat Res 1988; 113 (3) 473-486
  • 25 Ehmcke J, Luetjens CM, Schlatt S. Clonal organization of proliferating spermatogonial stem cells in adult males of two species of non-human primates, Macaca mulatta and Callithrix jacchus . Biol Reprod 2005; 72 (2) 293-300
  • 26 Ehmcke J, Simorangkir DR, Schlatt S. Identification of the starting point for spermatogenesis and characterization of the testicular stem cell in adult male rhesus monkeys. Hum Reprod 2005; 20 (5) 1185-1193
  • 27 Shinohara T, Avarbock MR, Brinster RL. beta1- and alpha6-integrin are surface markers on mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 1999; 96 (10) 5504-5509
  • 28 Kubota H, Avarbock MR, Brinster RL. Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci U S A 2003; 100 (11) 6487-6492
  • 29 Kanatsu-Shinohara M, Toyokuni S, Shinohara T. CD9 is a surface marker on mouse and rat male germline stem cells. Biol Reprod 2004; 70 (1) 70-75
  • 30 Buageaw A, Sukhwani M, Ben-Yehudah A , et al. GDNF family receptor alpha1 phenotype of spermatogonial stem cells in immature mouse testes. Biol Reprod 2005; 73 (5) 1011-1016
  • 31 Tokuda M, Kadokawa Y, Kurahashi H, Marunouchi T. CDH1 is a specific marker for undifferentiated spermatogonia in mouse testes. Biol Reprod 2007; 76 (1) 130-141
  • 32 Fujita K, Ohta H, Tsujimura A , et al. Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia. J Clin Invest 2005; 115 (7) 1855-1861
  • 33 Ohmura M, Yoshida S, Ide Y, Nagamatsu G, Suda T, Ohbo K. Spatial analysis of germ stem cell development in Oct-4/EGFP transgenic mice. Arch Histol Cytol 2004; 67 (4) 285-296
  • 34 Meng X, Lindahl M, Hyvönen ME , et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 2000; 287 (5457) 1489-1493
  • 35 Costoya JA, Hobbs RM, Barna M , et al. Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet 2004; 36 (6) 653-659
  • 36 Yoshida S, Takakura A, Ohbo K , et al. Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis. Dev Biol 2004; 269 (2) 447-458
  • 37 Raverot G, Weiss J, Park SY, Hurley L, Jameson JL. Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis. Dev Biol 2005; 283 (1) 215-225
  • 38 Sada A, Suzuki A, Suzuki H, Saga Y. The RNA-binding protein NANOS2 is required to maintain murine spermatogonial stem cells. Science 2009; 325 (5946) 1394-1398
  • 39 Giuili G, Tomljenovic A, Labrecque N, Oulad-Abdelghani M, Rassoulzadegan M, Cuzin F. Murine spermatogonial stem cells: targeted transgene expression and purification in an active state. EMBO Rep 2002; 3 (8) 753-759
  • 40 Sadate-Ngatchou PI, Payne CJ, Dearth AT, Braun RE. Cre recombinase activity specific to postnatal, premeiotic male germ cells in transgenic mice. Genesis 2008; 46 (12) 738-742
  • 41 Nakagawa T, Nabeshima Y, Yoshida S. Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. Dev Cell 2007; 12 (2) 195-206
  • 42 Reijo RA, Dorfman DM, Slee R , et al. DAZ family proteins exist throughout male germ cell development and transit from nucleus to cytoplasm at meiosis in humans and mice. Biol Reprod 2000; 63 (5) 1490-1496
  • 43 Yang J, Chai L, Fowles TC , et al. Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells. Proc Natl Acad Sci U S A 2008; 105 (50) 19756-19761
  • 44 Phillips BT, Gassei K, Orwig KE. Spermatogonial stem cell regulation and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 2010; 365 (1546) 1663-1678
  • 45 Grisanti L, Falciatori I, Grasso M , et al. Identification of spermatogonial stem cell subsets by morphological analysis and prospective isolation. Stem Cells 2009; 27 (12) 3043-3052
  • 46 Dym M, He Z, Jiang J, Pant D, Kokkinaki M. Spermatogonial stem cells: unlimited potential. Reprod Fertil Dev 2009; 21 (1) 15-21
  • 47 Conrad S, Renninger M, Hennenlotter J , et al. Generation of pluripotent stem cells from adult human testis. Nature 2008; 456 (7220) 344-349
  • 48 Izadyar F, Wong J, Maki C , et al. Identification and characterization of repopulating spermatogonial stem cells from the adult human testis. Hum Reprod 2011; 26 (6) 1296-1306
  • 49 Tran J, Brenner TJ, DiNardo S. Somatic control over the germline stem cell lineage during Drosophila spermatogenesis. Nature 2000; 407 (6805) 754-757
  • 50 Cheng CY, Mruk DD. Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiol Rev 2002; 82 (4) 825-874
  • 51 Oatley JM, Oatley MJ, Avarbock MR, Tobias JW, Brinster RL. Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 2009; 136 (7) 1191-1199
  • 52 Yoshida S, Sukeno M, Nabeshima Y. A vasculature-associated niche for undifferentiated spermatogonia in the mouse testis. Science 2007; 317 (5845) 1722-1726
  • 53 Ogawa T, Ohmura M, Ohbo K. The niche for spermatogonial stem cells in the mammalian testis. Int J Hematol 2005; 82 (5) 381-388
  • 54 De Rooij DG, Lok D. Regulation of the density of spermatogonia in the seminiferous epithelium of the Chinese hamster: II. Differentiating spermatogonia. Anat Rec 1987; 217 (2) 131-136
  • 55 Van Keulen CJG, de Rooij DG. Spermatogenic clones developing from repopulating stem cells surviving a high dose of an alkylating agent. I. First 15 days after injury. Cell Tissue Kinet 1975; 8: 543-551
  • 56 van Beek MEAB, Meistrich ML, de Rooij DG. Probability of self-renewing divisions of spermatogonial stem cells in colonies, formed after fission neutron irradiation. Cell Tissue Kinet 1990; 23 (1) 1-16
  • 57 Nagano M, Avarbock MR, Leonida EB, Brinster CJ, Brinster RL. Culture of mouse spermatogonial stem cells. Tissue Cell 1998; 30 (4) 389-397
  • 58 Nagano M, Shinohara T, Avarbock MR, Brinster RL. Retrovirus-mediated gene delivery into male germ line stem cells. FEBS Lett 2000; 475 (1) 7-10
  • 59 Kanatsu-Shinohara M, Ogonuki N, Inoue K , et al. Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol Reprod 2003; 69 (2) 612-616
  • 60 Kubota H, Avarbock MR, Brinster RL. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 2004; 101 (47) 16489-16494
  • 61 Kanatsu-Shinohara M, Ogonuki N, Iwano T , et al. Genetic and epigenetic properties of mouse male germline stem cells during long-term culture. Development 2005; 132 (18) 4155-4163
  • 62 Kanatsu-Shinohara M, Inoue K, Ogonuki N, Morimoto H, Ogura A, Shinohara T. Serum- and feeder-free culture of mouse germline stem cells. Biol Reprod 2011; 84 (1) 97-105
  • 63 Ryu BY, Kubota H, Avarbock MR, Brinster RL. Conservation of spermatogonial stem cell self-renewal signaling between mouse and rat. Proc Natl Acad Sci U S A 2005; 102 (40) 14302-14307
  • 64 Wu Z, Falciatori I, Molyneux LA, Richardson TE, Chapman KM, Hamra FK. Spermatogonial culture medium: an effective and efficient nutrient mixture for culturing rat spermatogonial stem cells. Biol Reprod 2009; 81 (1) 77-86
  • 65 Kanatsu-Shinohara M, Muneto T, Lee J , et al. Long-term culture of male germline stem cells from hamster testes. Biol Reprod 2008; 78 (4) 611-617
  • 66 Aponte PM, Soda T, Teerds KJ, Mizrak SC, van de Kant HJ, de Rooij DG. Propagation of bovine spermatogonial stem cells in vitro. Reproduction 2008; 136 (5) 543-557
  • 67 Sadri-Ardekani H, Mizrak SC, van Daalen SK , et al. Propagation of human spermatogonial stem cells in vitro. JAMA 2009; 302 (19) 2127-2134
  • 68 Sadri-Ardekani H, Akhondi MA, van der Veen F, Repping S, van Pelt AM. In vitro propagation of human prepubertal spermatogonial stem cells. JAMA 2011; 305 (23) 2416-2418
  • 69 Kanatsu-Shinohara M, Inoue K, Lee J , et al. Generation of pluripotent stem cells from neonatal mouse testis. Cell 2004; 119 (7) 1001-1012
  • 70 Guan K, Nayernia K, Maier LS , et al. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 2006; 440 (7088) 1199-1203
  • 71 Izadyar F, Pau F, Marh J , et al. Generation of multipotent cell lines from a distinct population of male germ line stem cells. Reproduction 2008; 135 (6) 771-784
  • 72 Kossack N, Meneses J, Shefi S , et al. Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells 2009; 27 (1) 138-149
  • 73 Ko K, Araúzo-Bravo MJ, Tapia N , et al. Human adult germline stem cells in question. Nature 2010; 465 (7301) E1; discussion E3
  • 74 Seandel M, James D, Shmelkov SV , et al. Generation of functional multipotent adult stem cells from GPR125+ germline progenitors. Nature 2007; 449 (7160) 346-350
  • 75 Geijsen N, Hochedlinger K. gPS navigates germ cells to pluripotency. Cell Stem Cell 2009; 5 (1) 3-4
  • 76 Hawkins MM, Stevens MC. The long-term survivors. Br Med Bull 1996; 52 (4) 898-923
  • 77 Bleyer WA. The impact of childhood cancer on the United States and the world. CA Cancer J Clin 1990; 40 (6) 355-367
  • 78 Aksglaede L, Wikström AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update 2006; 12 (1) 39-48
  • 79 Yamada K, Fujita K, Quan J , et al. Increased apoptosis of germ cells in patients with AZFc deletions. J Assist Reprod Genet 2010; 27 (6) 293-297
  • 80 de Rooij DG. The spermatogonial stem cell niche. Microsc Res Tech 2009; 72 (8) 580-585
  • 81 Schlatt S. Spermatogonial stem cell preservation and transplantation. Mol Cell Endocrinol 2002; 187 (1-2) 107-111
  • 82 Luetjens CM, Stukenborg JB, Nieschlag E, Simoni M, Wistuba J. Complete spermatogenesis in orthotopic but not in ectopic transplants of autologously grafted marmoset testicular tissue. Endocrinology 2008; 149 (4) 1736-1747
  • 83 Milazzo JP, Vaudreuil L, Cauliez B , et al. Comparison of conditions for cryopreservation of testicular tissue from immature mice. Hum Reprod 2008; 23 (1) 17-28
  • 84 Milazzo JP, Travers A, Bironneau A , et al. Rapid screening of cryopreservation protocols for murine prepubertal testicular tissue by histology and PCNA immunostaining. J Androl 2010; 31 (6) 617-630
  • 85 Shinohara T, Inoue K, Ogonuki N , et al. Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination. Hum Reprod 2002; 17 (12) 3039-3045
  • 86 Kvist K, Thorup J, Byskov AG, Høyer PE, Møllgård K, Yding Andersen C. Cryopreservation of intact testicular tissue from boys with cryptorchidism. Hum Reprod 2006; 21 (2) 484-491
  • 87 Keros V, Hultenby K, Borgström B, Fridström M, Jahnukainen K, Hovatta O. Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Hum Reprod 2007; 22 (5) 1384-1395
  • 88 Honaramooz A, Snedaker A, Boiani M, Schöler H, Dobrinski I, Schlatt S. Sperm from neonatal mammalian testes grafted in mice. Nature 2002; 418 (6899) 778-781
  • 89 Ohta H, Sakaide Y, Wakayama T. The birth of mice from testicular spermatozoa retrieved from frozen testicular sections. Biol Reprod 2008; 78 (5) 807-811
  • 90 Jahnukainen K, Ehmcke J, Hergenrother SD, Schlatt S. Effect of cold storage and cryopreservation of immature non-human primate testicular tissue on spermatogonial stem cell potential in xenografts. Hum Reprod 2007; 22 (4) 1060-1067
  • 91 Goossens E, Frederickx V, Geens M, De Block G, Tournaye H. Cryosurvival and spermatogenesis after allografting prepubertal mouse tissue: comparison of two cryopreservation protocols. Fertil Steril 2008; 89 (3) 725-727
  • 92 Zeng W, Snedaker AK, Megee S , et al. Preservation and transplantation of porcine testis tissue. Reprod Fertil Dev 2009; 21 (3) 489-497
  • 93 Abrishami M, Anzar M, Yang Y, Honaramooz A. Cryopreservation of immature porcine testis tissue to maintain its developmental potential after xenografting into recipient mice. Theriogenology 2010; 73 (1) 86-96
  • 94 Curaba M, Verleysen M, Amorim CA , et al. Cryopreservation of prepubertal mouse testicular tissue by vitrification. Fertil Steril 2011; 95 (4) 1229-1234 , e1
  • 95 Baert Y, Goossens E, Van Saen D , et al. Orthotopic grafting of cryopreserved prepubertal testicular tissue: in search of a simple yet effective cryopreservation protocol. Fertil Steril 2012; 97 (5) 1152-1157
  • 96 Parreira GG, Ogawa T, Avarbock MR, França LR, Brinster RL, Russell LD. Development of germ cell transplants in mice. Biol Reprod 1998; 59 (6) 1360-1370
  • 97 Avarbock MR, Brinster CJ, Brinster RL. Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat Med 1996; 2 (6) 693-696
  • 98 Schlatt S, Rosiepen G, Weinbauer GF, Rolf C, Brook PF, Nieschlag E. Germ cell transfer into rat, bovine, monkey and human testes. Hum Reprod 1999; 14 (1) 144-150
  • 99 Honaramooz A, Behboodi E, Blash S, Megee SO, Dobrinski I. Germ cell transplantation in goats. Mol Reprod Dev 2003; 64 (4) 422-428
  • 100 Mikkola M, Sironen A, Kopp C , et al. Transplantation of normal boar testicular cells resulted in complete focal spermatogenesis in a boar affected by the immotile short-tail sperm defect. Reprod Domest Anim 2006; 41 (2) 124-128
  • 101 Kim Y, Turner D, Nelson J, Dobrinski I, McEntee M, Travis AJ. Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog. Reproduction 2008; 136 (6) 823-831
  • 102 Hermann BP, Sukhwani M, Hansel MC, Orwig KE. Spermatogonial stem cells in higher primates: are there differences from those in rodents?. Reproduction 2010; 139 (3) 479-493
  • 103 Dobrinski I, Avarbock MR, Brinster RL. Transplantation of germ cells from rabbits and dogs into mouse testes. Biol Reprod 1999; 61 (5) 1331-1339
  • 104 Ogawa T, Dobrinski I, Avarbock MR, Brinster RL. Xenogeneic spermatogenesis following transplantation of hamster germ cells to mouse testes. Biol Reprod 1999; 60 (2) 515-521
  • 105 Goossens E, Frederickx V, De Block G, Van Steirteghem AC, Tournaye H. Reproductive capacity of sperm obtained after germ cell transplantation in a mouse model. Hum Reprod 2003; 18 (9) 1874-1880
  • 106 Goossens E, De Block G, Tournaye H. Computer-assisted motility analysis of spermatozoa obtained after spermatogonial stem cell transplantation in the mouse. Fertil Steril 2008; 90 (4, Suppl) 1411-1416
  • 107 Goossens E, De Rycke M, Haentjens P, Tournaye H. DNA methylation patterns of spermatozoa and two generations of offspring obtained after murine spermatogonial stem cell transplantation. Hum Reprod 2009; 24 (9) 2255-2263
  • 108 Goossens E, de Vos P, Tournaye H. 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 2010; 25 (7) 1836-1842
  • 109 Goossens E, Bilgec T, Van Saen D, Tournaye H. Mouse germ cells go through typical epigenetic modifications after intratesticular tissue grafting. Hum Reprod 2011; 26 (12) 3388-3400
  • 110 Honaramooz A, Snedaker A, Boiani M, Schöler H, Dobrinski I, Schlatt S. Sperm from neonatal mammalian testes grafted in mice. Nature 2002; 418 (6899) 778-781
  • 111 Schlatt S, Honaramooz A, Boiani M, Schöler HR, Dobrinski I. Progeny from sperm obtained after ectopic grafting of neonatal mouse testes. Biol Reprod 2003; 68 (6) 2331-2335
  • 112 Honaramooz A, Li MW, Penedo MC, Meyers S, Dobrinski I. Accelerated maturation of primate testis by xenografting into mice. Biol Reprod 2004; 70 (5) 1500-1503
  • 113 Schlatt S, Kim S, Gosden R. Spermatogenesis and steroidogenesis in mouse, hamster and monkey testicular tissue after cryopreservation and grafting. Reproduction 2002; 124: 323-329
  • 114 Oatley JM, de Avila DM, Reeves JJ, McLean DJ. Spermatogenesis and germ cell transgene expression in xenografted bovine testicular tissue. Biol Reprod 2004; 71 (2) 494-501
  • 115 Geens M, De Block G, Goossens E, Frederickx V, Van Steirteghem AC, Tournaye H. Spermatogonial survival after grafting human testicular tissue to immunodeficient mice. Hum Reprod 2006; 21 (2) 390-396
  • 116 Schlatt S, Honaramooz A, Ehmcke J , et al. Limited survival of adult human testicular tissue as ectopic xenograft. Hum Reprod 2006; 21 (2) 384-389
  • 117 Sato Y, Nozawa S, Yoshiike M, Arai M, Sasaki C, Iwamoto T. Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation. Hum Reprod 2010; 25 (5) 1113-1122
  • 118 Wyns C, Van Langendonckt A, Wese FX, Donnez J, Curaba M. Long-term spermatogonial survival in cryopreserved and xenografted immature human testicular tissue. Hum Reprod 2008; 23 (11) 2402-2414
  • 119 Shinohara T, Inoue K, Ogonuki N , et al. Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination. Hum Reprod 2002; 17 (12) 3039-3045
  • 120 Van Saen D, Goossens E, De Block G, Tournaye H. Regeneration of spermatogenesis by grafting testicular tissue or injecting testicular cells into the testes of sterile mice: a comparative study. Fertil Steril 2009; 91 (5, Suppl) 2264-2272
  • 121 Jahnukainen K, Hou M, Petersen C, Setchell B, Söder O. Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. Cancer Res 2001; 61 (2) 706-710
  • 122 Fujita K, Ohta H, Tsujimura A , et al. Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia. J Clin Invest 2005; 115 (7) 1855-1861
  • 123 Fujita K, Tsujimura A, Miyagawa Y , et al. 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 2006; 66 (23) 11166-11171
  • 124 Geens M, Van de Velde H, De Block G, Goossens E, Van Steirteghem A, Tournaye H. The efficiency of magnetic-activated cell sorting and fluorescence-activated cell sorting in the decontamination of testicular cell suspensions in cancer patients. Hum Reprod 2007; 22 (3) 733-742
  • 125 Geens M, Goossens E, Tournaye H. Cell selection by selective matrix adhesion is not sufficiently efficient for complete malignant cell depletion from contaminated human testicular cell suspensions. Fertil Steril 2011; 95 (2) 787-791
  • 126 Glaser T, Opitz T, Kischlat T , et al. Adult germ line stem cells as a source of functional neurons and glia. Stem Cells 2008; 26 (9) 2434-2443
  • 127 Streckfuss-Bömeke K, Vlasov A, Hülsmann S , et al. Generation of functional neurons and glia from multipotent adult mouse germ-line stem cells. Stem Cell Res (Amst) 2009; 2 (2) 139-154
  • 128 Guan K, Wagner S, Unsöld B , et al. Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells. Circ Res 2007; 100 (11) 1615-1625
  • 129 Simon L, Ekman GC, Kostereva N , et al. Direct transdifferentiation of stem/progenitor spermatogonia into reproductive and nonreproductive tissues of all germ layers. Stem Cells 2009; 27 (7) 1666-1675
  • 130 Ning L, Goossens E, Geens M , et al. Mouse spermatogonial stem cells obtain morphologic and functional characteristics of hematopoietic cells in vivo. Hum Reprod 2010; 25 (12) 3101-3109
  • 131 Baeyens L, Bouwens L. Can beta-cells be derived from exocrine pancreas?. Diabetes Obes Metab 2008; 10 (Suppl. 04) 170-178
  • 132 Eberhard D, Tosh D. Transdifferentiation and metaplasia as a paradigm for understanding development and disease. Cell Mol Life Sci 2008; 65 (1) 33-40
  • 133 Kanatsu-Shinohara M, Shinohara T. The germ of pluripotency. Nat Biotechnol 2006; 24 (6) 663-664
  • 134 Izadyar F, Pau F, Marh J , et al. Generation of multipotent cell lines from a distinct population of male germ line stem cells. Reproduction 2008; 135 (6) 771-784
  • 135 Nagano M, Shinohara T, Avarbock MR, Brinster RL. Retrovirus-mediated gene delivery into male germ line stem cells. FEBS Lett 2000; 475 (1) 7-10
  • 136 Kanatsu-Shinohara M, Toyokuni S, Shinohara T. Transgenic mice produced by retroviral transduction of male germ line stem cells in vivo. Biol Reprod 2004; 71 (4) 1202-1207