Spermatogonial Kök Hücre / Spermatogonial Stem Cell
Spermatogonial kök hücreler (SKH) testiste bulunan bir çeşit yetişkin kök hücre türüdür. Kendini yenileme ve farklanma kapasitesine sahip olan bu hücreler pluripotent özellikte olup yetişkindeki diğer kök hücreleri arasında gelecek nesile genetik olarak katkı sağlayacak tek hücre çeşidi olması özelliği ile eşsizdir. Son yıllarda deney hayvanları ve insan SKH’nin izolasyonu, karakterizasyonu ve transplantasyonu üzerine yapılan pek çok çalışma bu hücrelerin biyolojisini anlamayı sağlamış, reprodüktif ve rejeneratif tıptaki geniş kullanım alanlarına dikkat çekmiştir. Özellikle erkek infertilitesi tedavisi konusunda yapılmış olan araştırmalar umut vadeden niteliktedir. Ancak testiste bulunan SKH miktarının çok az olması hücre kültürü çalışmalarını daha önemli hale getirmektedir. Yüksek saflıkta ve canlılıkta hücreleri güvenli bir şekilde izole etmek ve nakledebilmek, karşılaşılan en büyük güçlükler olmakla birlikte bu süreçteki en önemli basamaklardır. İnsan SKH hattının geliştirilmesi ve kültürde tam bir başarı sağlanması yapılacak çalışmaları hızlandıracak ve daha farklı bir boyuta taşıyacaktır.
Anahtar Kelimeler: Sperm, Kök Hücre, İzolasyon, Spermatogenez, İnfertilite
Spermatogonial stem cells (SSC) found in male testis is a kind of adult stem cell. These pluripotent cells having self-renewal and differentiation capacity are unique since they genetically contribute to the next generation. Recent studies which have been done on the isolation, characterization and transplantation of SSCs enabled to understand SSC biology and its usage in reproductive and regenerative medicine. Especially studies related to male infertility are quite promising. However, the low amount of SSCs in the testis makes cell culture studies more crucial. Isolating and transplanting cells at high purity and vitality are the most difficult challenges but also the most important steps. Development of a steady and reliable human SSC line and having success in the culture will accelerate SSC studies.
Keywords: Sperm, Stem Cell, Isolation, Spermatogenesis, Infertility
Brinster RL and Zimmermann JW. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci USA. 1994; 91:11298–302.
Brinster RL and Avarbock MR. Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci USA. 1994; 91:11303–7.
Kubota H, Avarbock MR, Brinster RL. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci USA. 2004; 101:16489–94.
Glaser T, Opitz T, Kischlat T, et al. Adult germ line stem cells as a source of functional neurons and glia. Stem Cells. 2008; 26:2434-43.
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; 135:771-84.
Seandel M, James D, Shmelkov SV, et al. Generation of functional multipotent adult stem cells from GPR125+germline progenitors. Nature. 2007; 449:346-50.
Guan K, Nayernia K, Maier LS, et al. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature. 2006; 440:1199-203.
Kubota H, Brinster RL. Technology Insight: in vitro culture of spermatogonial stem cells and their potential therapeutic uses. Nat Clin Pract Endocrinol Metab.2006; 2:99-108.
Liu X, Wu H, Loring J,et al. Trisomy eight in ES cells is a common potential problem in gene targeting and interferes with germ line transmission. Dev Dyn. 1997; 209:85–91.
Longo L, Bygrave A, Grosveld FG, Pandolfi P. P. The chromosome make-up of mouse embryonic stem cells is predictive of somatic and germ cell chimaerism. Transgenic Res. 1997; 6:321–8.
Humpherys D, Eggan K, Akutsu H, et al. Epigenetic instability in ES cells and cloned mice. Science. 2001; 293:95–7.
T.W.Sadler. Gametogenez: Germ hücrelerinin Erkek ve Dişi Gametlere Dönüşmesi. Langman Medikal Embriyoloji. 2011; 11. baskıdan çeviri. Palme Yayıncılık.
McCarrey JR. Development of the germ cell. In: Cell and Molecular Biology of the Testis. 1993; pp 58–89. Oxford University Press, Oxford, UK.
Nayernia K, Lee JH, Drusenheimer N, et al. Derivation of male germ cells from bone marrow stem cells. Lab Invest. 2006; 86:654–63.
Massimo De Felici. Origin, Migration, and Proliferation of Human Primordial Germ Cells. G. Coticchio et al. eds. Oogenesis. 2013; pp 19-37. Springer London.
Dym M. Spermatogonial stem cells of the testis. Proc Natl Acad Sci USA. 1994; 91:11287–9.
Dadoune JP. New insights into male gametogenesis: what about the spermatogonial stem cell niche? Folia Histochem. Cytobiol. 2007; 45:141–147.
Dym M, Kokkinaki M, He Z. Spermatogonial stem cells: mouse and human comparisons. Birth Defects Res. 2009; 87:27–34.
He Z, Kokkinaki M, Jiang J, Dobrinski I, Dym M. Isolation, characterization, and culture of human spermatogonia. Biol Reprod. 2010; 82:363–72.
Meng X, Lindahl M, Hyvonen ME, et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science. 2000; 287:1489–93.
Zheng K, Wu X, Kaestner KH, Wang PJ. The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse. BMC Dev Biol. 2009; 9:1–11.
van Bragt MP, Roepers-Gajadien HL, Korver CM, et al. Expression of the pluripotency marker UTF1 is restricted to a subpopulation of early A spermatogonia in rat testis. Reproduction. 2008; 136:33–40.
Gassei K, Orwig KE. SALL4 expression in gonocytes and spermatogonial clones of postnatal mouse testes. 2013; PLoS ONE. 8:e53976.
Wang YL, Liu W, Sun YJ, et al. Overexpression of ubiquitin carboxyl-terminal hydrolase L1 arrests spermatogenesis in transgenic mice. Mol Reprod Dev. 2006; 73:40–9.
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; 283:215–25.
Chen B, Wang YB, Zhang ZL, et al. Xeno-free culture of human spermatogonial stem cells supported by human embryonic stem cell-derived fibroblast-like cells. Asian J Androl. 2009; 11:557–65.
Prof. Dr. Kaan AYDOS. Androloji’nin yeni bir uğraş alanı; Spermatogonial Kök Hücre Nakli. Ankara Üniversitesi Tıp Fakültesi İnfertilite Araştırma ve Uygulama Merkezi
Barzon L et al. New perspectives for gene therapy in endocrinology. Eur J Endocrinol. 2000; 143:447–66
MIAO Xiang-yang. Production of Transgenic Animals Using Spermatogonial Stem Cells. Agricultural Sciences in China. 2011; 10(5):762-8.
Nagano M, Brinster CJ, Orwig KE, Ryu BY, Avarbock MR, Brinster RL. Transgenic mice produced by retroviral transduction of male germ-line stem cells. Proc Natl Acad Sci USA. 2001; 98:13090–5.
Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nature Med. 2008; 14(11):1197–213.
Itman C, Mendis S, Barakat B, Loveland KL. All in the family: TGF-β family action in testis development. Reproduction. 2006; 132(2):233–46.
Boekelheide K. Mechanisms of toxic damage to spermatogenesis. J Natl Cancer Inst Monogr. 2005; 34:6–8.
L.R. Schover, K. Brey, A. Lichtin, L.I. Lipshultz, S. Jeha. Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. J Clin Oncol. 2002; 20:1880–9
Guo Y, Hai Y, Gong Y, Li Z, He Z. Characterization, isolation, and culture of mouse and human spermatogonial stem cells. J Cell Physiol. 2014; 229(4):407-13.
Ogawa T, Dobrinski I, Avarbock MR, Brinster RL. Transplantation of male germ line stem cells restores fertility in infertile mice. Nat Med. 2000, 6:29–34
Hermann BP, Sukhwani M, Winkler F, et al. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. Cell Stem Cell. 2012; 11:715–26.
Richardson TE, Chapman KM, Tenenhaus Dann C, Hammer RE, Hamra FK. Sterile testis complementation with spermatogonial lines restores fertility to DAZL-deficient rats and maximizes donor germline transmission. PLoS One. 2009; 4:6308
Shinohara T, Orwig KE, Avarbock ME, Brinster RL. Remodeling of the postnatal mouse testis is accompanied by dramatic changes in stem cell number and niche accessibility. Proc Natl Acad Sci USA. 2001; 98:6186–91.
Brinster CJ, Ryu BY, Avarbock MR, Karagenc L, Brinster RL, Orwig KE. Restoration of fertility by germ cell transplantation requires effective recipient preparation. Biol Reprod. 2003; 69:412–20.
Honaramooz A, Behboodi E, Megee SO, et al. Fertility and germline transmission of donor haplotype following germ cell transplantation in immunocompetent goats. Biol Reprod. 200369:1260–4.
Izadyar F, Den Ouden K, Stout T, et al. Autologous and homologous transplantation of bovine spermatogonial stem cells. Reproduction. 2003; 126:765–74.
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; 41:124–8.
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; 136:823–31.
Herrid M, Olejnik J, Jackson M, et al. Irradiation enhances the efficiency of testicular germ cell transplantation in sheep. Biol Reprod. 2009; 81:898–905.
Schlatt S, Foppiani L, Rolf C, Weinbauer GF, Nieschlag E. Germ cell transplantation into X-irradiated monkey testes. Hum Reprod. 2002; 17:55–62.
Jahnukainen K, Ehmcke J, Quader MA, et al. Testicular recovery after irradiation differs in prepubertal and pubertal non-human primates, and can be enhanced by autologous germ cell transplantation. Hum Reprod. 2011; 26:1945–54.
Kanatsu-Shinohara M, N. Ogonuki, K. Inoue, et al. Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol Reprod. 2003; 69:612–6.
Dobrinski I, Avarbock MR, Brinster RL. Germ cell transplantation from large domestic animals into mouse testes. Mol Reprod Dev. 2000; 57:270–9.
G. Shetty, Uthamanthil RK, W. Zhou, et al. Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys. Andrology. 2013; 1:886–98.
Nagano M, Patrizio P, Brinster RL. Long-term survival of human spermatogonial stem cells in mouse testes. Fertil Steril. 2002; 78:1225-33.
Kanatsu-Shinohara M, Toyokuni S, Morimoto T, Matsui S, Honjo T, Shinohara T. Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation. Biol Reprod. 2003; 68:1801–7.
Meistrich ML, Bruce WR, Clermont Y. Cellular composition of fractions of mouse testis cells following velocity sedimentation separation. Exp Cell Res. 1973; 79:213-27.
Barcellona WJ, Meistrich ML. Ultrastructural integrity of mouse testicular cells separated by velocity sedimentation. J Reprod Fertil. 1977; 50:61-8.
Zheng Y, Zhang Y, Qu R, He Y, Tian X, Zeng W. Spermatogonial stem cells from domestic animals: progress and prospects. Reproduction. 2014; 147:R65–R74.
Grabske RJ, Lake S, Gledhill BL, Meistrich ML. Centrifugal elutriation: separation of spermatogenic cells on the basis of sedimentation velocity. J Cell Physiol. 1975; 86:177-89.
Meistrich ML, Trostle PK. Separation of mouse testis cells by equilibrium density centrifugation in renografin gradients. Exp Cell Res. 1975; 92:231-44.
Bellve AR, Cavicchia JC, Millette CF, O’Brien DA, Bhatnagar YM, Dym M. Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization. J Cell Biol. 1977; 74:68-85.
Pedro Manuel Aponte. Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine. World J Stem Cells. 2015; 26; 7(4):669–80.
Orwig, KE, Avarbock MR, Brinster RL. Retrovirus-mediated modification of male germline stem cells in rats. Biol Reprod. 2002; 67:874–9.
Kanatsu-Shinohara M, Ogonuki N, Iwano T, et al. Genetic and epigenetic properties of mouse male germline stem cells during long-term culture. Development. 2005b; 132:4155–63.
Jeong D, McLean DJ, Griswold MD. Long-term culture and transplantation of murine testicular germ cells. J Androl. 2003; 24:661-9.
Dirami G, Ravindranath N, Pursel V, Dym M. Effects of stem cell factor and granulocyte macrophage-colony stimulating factor on survival of porcine type A spermatogonia cultured in KSOM. Biol Reprod. 1999; 61:225-30.
Hou J, Niu M, Liu L, et al. Establishment and Characterization of Human Germline Stem Cell Line with Unlimited Proliferation Potentials and no Tumor Formation. Sci Rep. 2015; 20; 5:16922.
Hanna Valli, Bart T. Phillips, Kyle E. Orwig, Kathrin Gassei, Makoto C. Nagano. Spermatogonial Stem Cells and Spermatogenesis. Knobil and Neill's Physiology of Reproduction Fourth Edition. Pages 595-635.
Honaramooz A, Yang Y. Recent advances in application of male germ cell transplantation in farm animals. Vet Med Int. 2010; 2011: pii: 657860.
Clouthier DE, Avarbock MR, Maika SD, Hammer RE, Brinster RL. Rat spermatogenesis in mouse testis. Nature. 1996; 381:418–21.
Ogawa T, Dobrinski I, Avarbock MR, Brinster RL. Xenogeneic spermatogenesis following transplantation of hamster germ cells to mouse testes. Biol Reprod. 1999; 60:515-21.
Radford J, Shalet S, Lieberman B. Fertility after treatment for cancer. BMJ. 1999; 319:935–6.
Brook PF, Radford JA, Shalet SM, Joyce AD, Gosden RG. Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation. Fertil Steril. 2001; 75:269–74.
Radford J. Restoration of fertility after treatment for cancer. Horm Res. 2003; 59(Suppl 1):21–3.
Wyns C, Curaba M, Petit S, et al. Management of fertility preservation in prepubertal patients: 5 years' experience at the Catholic University of Louvain. Hum Reprod. 2011; 26:737–47.
Ginsberg JP. New advances in fertility preservation for pediatric cancer patients. Curr Opin Pediatr. 2011; 23:9–13.
Sadri-Ardekani H, Mizrak SC, van Daalen SK, et al. Propagation of human spermatogonial stem cells in vitro. JAMA. 2009; 302:2127–34.
Ogawa T, Arechaga JM, Avarbock MR, Brinster RL. Transplantation of testis germinal cells into mouse seminiferous tubules. Int J Dev Biol. 1997; 41:111–22.
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; 14:144–50.
Faes K, Tournaye H, Goethals L, Lahoutte T, Hoorens A, Goossens E. Testicular cell transplantation into the human testes. Fertil Steril. 2013; 100:981–8.
Dobrinski I, Ogawa T, Avarbock MR, Brinster RL. Computer assisted image analysis to assess colonization of recipient seminiferous tubules by spermatogonial stem cells from transgenic donor mice. Mol Reprod Dev. 1999; 53:142-8.
Goossens E, Van Saen D, Tournaye H. Spermatogonial stem cell preservation and transplantation: from research to clinic. Hum Reprod. 2013; 28 (4): 897-907.
Avarbock MR, Brinster CJ, Brinster RL. Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat Med. 1996; 2:693-6.
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; 305:2416–8.
Wu X, Goodyear SM, Abramowitz LK, et al. Fertile offspring derived from mouse spermatogonial stem cells cryopreserved for more than 14 years. Hum Reprod. 2013; 27:1249–59.
Baert Y, Goossens E, van Saen D, Ning L, In't Veld P, Tournaye H. Orthotopic grafting of cryopreserved prepubertal testicular tissue: in search of a simple yet effective cryopreservation protocol, Fertil Steril. 2012; 97:1152-7.
Curaba M, Poels J, van Langendonckt A, Donnez J, Wyns C. Can prepubertal human testicular tissue be cryopreserved by vitrification. Fertil Steril. 2011; 95:2123.
Wu X, Schmidt JA, Avarbock MR, et al. Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc Natl Acad Sci USA, 2009; 106:21672–7
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; 115:1855–61.
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; 66:11166–71.
Hou M, Andersson M, Zheng C, Sundblad A, Soder O, Jahnukainen K. Decontamination of leukemic cells and enrichment of germ cells from testicular samples from rats with Roser's T-cell leukemia by flow cytometric sorting. Reproduction. 2007; 134:767–79.
Dovey SL, Valli H, Hermann BP, et al. Eliminating malignant contamination from therapeutic human spermatogonial stem cells. J Clin Invest. 2013; 123:1833–43.
Hermann BP, Sukhwani M, Salati J, Sheng Y, Chu T, Orwig KE. Separating spermatogonia from cancer cells in contaminated prepubertal primate testis cell suspensions. Hum Reprod. 2011; 26:3222–31.
Clermont Y. Renewal of spermatogonia in man. Am J Anat. 1966; 118:509-24.
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; 22:733–42.
- Şu halde refbacks yoktur.
This work is licensed under a Creative Commons Attribution 3.0 License.