Comparison of Hematopoietic and Spermatogonial Stem Cell Niches from the Regenerative Medicine Aspect

  • Sevil Köse
  • Nilgün Yersal
  • Selin Önen
  • Petek KorkusuzEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1107)


Recent advances require a dual evaluation of germ and somatic stem cell niches with a regenerative medicine perspective. For a better point of view of the niche concept, it is needed to compare the microenvironments of those niches in respect to several components. The cellular environment of spermatogonial stem cells’ niche consists of Sertoli cells, Leydig cells, vascular endothelial cells, epididymal fat cells, peritubular myoid cells while hematopoietic stem cells have mesenchymal stem cells, osteoblasts, osteoclasts, megacaryocytes, macrophages, vascular endothelial cells, pericytes and adipocytes in their microenvironment. Not only those cells’, but also the effect of the other factors such as hormones, growth factors, chemokines, cytokines, extracellular matrix components, biomechanical forces (like shear stress, tension or compression) and physical environmental elements such as temperature, oxygen level and pH will be clarified during the chapter. Because it is known that the microenvironment has an important role in the stem cell homeostasis and disease conditions, it is crucial to understand the details of the microenvironment and to be able to compare the niche concepts of the different types of stem cells from each other, for the regenerative interventions. Indeed, the purpose of this chapter is to point out the usage of niche engineering within the further studies in the regenerative medicine field. Decellularized, synthetic or non-synthetic scaffolds may help to mimic the stem cell niche. However, the shared or different characteristics of germ and somatic stem cell microenvironments are necessary to constitute a proper niche model. When considered from this aspect, it is possible to produce some strategies on the personalized medicine by using those artificial models of stem cell microenvironment.


Bone marrow niche Hematopoietic stem cell Microenvironment Niche Regeneration Spermatogonial stem cell 



2 arachidonoyl glycerol


Androgen Binding Protein


A Disintegrin and Metalloprotease


(anandamide), N-arachidonoyl ethanolamine




Bisphenol A Diglycidyl Ether


Basic Fibroblast Growth Factor


Bone Morphogenetic Protein


Blood Testis Barrier


Cannabinoid receptor targets type-1


Cannabinoid receptor targets type-2


C-type lectin-like receptor-2


Central Nervous System


Colony Stimulating factor 1


CSF1 Receptor


Chemokine (C-X-C motif) ligand 12


Chemokine receptor type 4


Endothelial Cell


Extracellular Matrix






Epididymal White Adipose Tissue


Fatty Acid Amide hydrolase


Fibroblast Growth Factor


FGF Receptor 2


Follicle-Stimulating Hormone


Granulocyte Colony-Stimulating Factor


Glial cell-line Derived Neutrophic Factor


GDNF-Family Receptor α1


G Protein-Coupled Receptors


Human Chorionic Gonadotropin


Hematopoietic Stem Cells


Hematopoietic Stem/Progenitor Cells


Interstitial Macrophage


Kinase Insert Domain Receptor


Leydig Cell


Luteinizing Hormone


Monoacylglycerol lipase


Mitogen-Activated Protein Kinase


Mouse Embryonic Fibroblast


Matrix Metalloproteinases


Mesenchymal Stem Cells


Nestin Positive


Nitric Oxide


Primordial Germ Cell


Peritubular Macrophage


Peritubular Myoid Cell




Proliferator-Activated Receptor-γ


Parathyroid hormone protein receptor


Retinoic acid


Receptor Tyrosine Kinase


Runx2 high


Sertoli Cell


Stem Cell Factor (KIT ligand)


Src Family Kinase


Spermatogonial Stem Cell


SIM mouse embryo-derived thioquanine – and- quabian –resistant cells


Tight Junction




Vascular Endothelial


Vascular Endothelial Growth Factor


Vascular Endothelial Growth Factor Receptor-2


  1. Adamo L, Naveiras O, Wenzel PL, McKinney-Freeman S, Mack PJ, Gracia-Sancho J, Suchy-Dicey A, Yoshimoto M, Lensch MW, Yoder MC, Garcia-Cardena G, Daley GQ (2009) Biomechanical forces promote embryonic haematopoiesis. Nature 459(7250):1131–1135. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Asada N, Katayama Y (2014) Regulation of hematopoiesis in endosteal microenvironments. Int J Hematol 99(6):679–684. CrossRefPubMedGoogle Scholar
  3. Asada N, Takeishi S, Frenette PS (2017) Complexity of bone marrow hematopoietic stem cell niche. Int J Hematol 106(1):45–54. CrossRefPubMedGoogle Scholar
  4. Baert Y, De Kock J, Alves-Lopes JP, Soder O, Stukenborg JB, Goossens E (2017) Primary human testicular cells self-organize into organoids with testicular properties. Stem Cell Reports 8(1):30–38. CrossRefPubMedGoogle Scholar
  5. Bardelli S, Moccetti M (2017) Remodeling the human adult stem cell niche for regenerative medicine applications. Stem Cells Int 2017:6406025. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Battiwalla M, Hematti P (2009) Mesenchymal stem cells in hematopoietic stem cell transplantation. Cytotherapy 11(5):503–515. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Beiermeister KA, Keck BM, Sifri ZC, ElHassan IO, Hannoush EJ, Alzate WD, Rameshwar P, Livingston DH, Mohr AM (2010) Hematopoietic progenitor cell mobilization is mediated through beta-2 and beta-3 receptors after injury. J Trauma 69(2):338–343. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bello AB, Park H, Lee SH (2018) Current approaches in biomaterial-based hematopoietic stem cell niches. Acta Biomater.
  9. Bhat GK, Sea TL, Olatinwo MO, Simorangkir D, Ford GD, Ford BD, Mann DR (2006) Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse. J Androl 27(2):302–310. CrossRefPubMedGoogle Scholar
  10. Bruns I, Lucas D, Pinho S, Ahmed J, Lambert MP, Kunisaki Y, Scheiermann C, Schiff L, Poncz M, Bergman A, Frenette PS (2014) Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nat Med 20(11):1315–1320. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Butler JM, Nolan DJ, Vertes EL, Varnum-Finney B, Kobayashi H, Hooper AT, Seandel M, Shido K, White IA, Kobayashi M, Witte L, May C, Shawber C, Kimura Y, Kitajewski J, Rosenwaks Z, Bernstein ID, Rafii S (2010) Endothelial cells are essential for the self-renewal and repopulation of notch-dependent hematopoietic stem cells. Cell Stem Cell 6(3):251–264. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden DT (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425(6960):841–846. CrossRefPubMedGoogle Scholar
  13. Calvi LM, Bromberg O, Rhee Y, Weber JM, Smith JN, Basil MJ, Frisch BJ, Bellido T (2012) Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells. Blood 119(11):2489–2499. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Cantú AV, Laird DJ (2017) Primordial germ cell migration and the Wnt signaling pathway. Anim Reprod 14(1):89–101. CrossRefGoogle Scholar
  15. Cantu AV, Altshuler-Keylin S, Laird DJ (2016) Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling. J Cell Biol 214(2):215–229. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Chang MK, Raggatt LJ, Alexander KA, Kuliwaba JS, Fazzalari NL, Schroder K, Maylin ER, Ripoll VM, Hume DA, Pettit AR (2008) Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol 181(2):1232–1244CrossRefGoogle Scholar
  17. Chassot AA, Le Rolle M, Jourden M, Taketo MM, Ghyselinck NB, Chaboissier MC (2017) Constitutive WNT/CTNNB1 activation triggers spermatogonial stem cell proliferation and germ cell depletion. Dev Biol 426(1):17–27. CrossRefPubMedGoogle Scholar
  18. Chitteti BR, Cheng YH, Streicher DA, Rodriguez-Rodriguez S, Carlesso N, Srour EF, Kacena MA (2010) Osteoblast lineage cells expressing high levels of Runx2 enhance hematopoietic progenitor cell proliferation and function. J Cell Biochem 111(2):284–294. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Choi JS, Harley BA (2012) The combined influence of substrate elasticity and ligand density on the viability and biophysical properties of hematopoietic stem and progenitor cells. Biomaterials 33(18):4460–4468. CrossRefPubMedGoogle Scholar
  20. Choi JS, Mahadik BP, Harley BA (2015) Engineering the hematopoietic stem cell niche: Frontiers in biomaterial science. Biotechnol J 10(10):1529–1545. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Chouinard-Pelletier G, Jahnsen ED, Jones EA (2013) Increased shear stress inhibits angiogenesis in veins and not arteries during vascular development. Angiogenesis 16(1):71–83. CrossRefPubMedGoogle Scholar
  22. Chow A, Lucas D, Hidalgo A, Mendez-Ferrer S, Hashimoto D, Scheiermann C, Battista M, Leboeuf M, Prophete C, van Rooijen N, Tanaka M, Merad M, Frenette PS (2011) Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med 208(2):261–271. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Christopher MJ, Liu F, Hilton MJ, Long F, Link DC (2009) Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization. Blood 114(7):1331–1339. CrossRefPubMedPubMedCentralGoogle Scholar
  24. de Rooij DG (2017) The nature and dynamics of spermatogonial stem cells. Development 144(17):3022–3030. CrossRefPubMedGoogle Scholar
  25. DeFalco T, Potter SJ, Williams AV, Waller B, Kan MJ, Capel B (2015) Macrophages contribute to the Spermatogonial niche in the adult testis. Cell Rep 12(7):1107–1119. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Dharampuriya PR, Scapin G, Wong C, John Wagner K, Cillis JL, Shah DI (2017) Tracking the origin, development, and differentiation of hematopoietic stem cells. Curr Opin Cell Biol 49:108–115. CrossRefPubMedGoogle Scholar
  27. DiMascio L, Voermans C, Uqoezwa M, Duncan A, Lu D, Wu J, Sankar U, Reya T (2007) Identification of adiponectin as a novel hemopoietic stem cell growth factor. J Immunol 178(6):3511–3520CrossRefGoogle Scholar
  28. Dong L, Hao H, Han W, Fu X (2015a) The role of the microenvironment on the fate of adult stem cells. Sci China Life Sci 58(7):639–648. CrossRefPubMedGoogle Scholar
  29. Dong WL, Tan FQ, Yang WX (2015b) Wnt signaling in testis development: unnecessary or essential? Gene 565(2):155–165. CrossRefPubMedGoogle Scholar
  30. Eslahi N, Hadjighassem MR, Joghataei MT, Mirzapour T, Bakhtiyari M, Shakeri M, Pirhajati V, Shirinbayan P, Koruji M (2013) The effects of poly L-lactic acid nanofiber scaffold on mouse spermatogonial stem cell culture. Int J Nanomedicine 8:4563–4576. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Esteves SC (2015) Clinical management of infertile men with nonobstructive azoospermia. Asian J Androl 17(3):459–470. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Even-Ram S, Artym V, Yamada KM (2006) Matrix control of stem cell fate. Cell 126(4):645–647. CrossRefPubMedGoogle Scholar
  33. Fasshauer M, Bluher M (2015) Adipokines in health and disease. Trends Pharmacol Sci 36(7):461–470. CrossRefPubMedGoogle Scholar
  34. Florian MC, Dorr K, Niebel A, Daria D, Schrezenmeier H, Rojewski M, Filippi MD, Hasenberg A, Gunzer M, Scharffetter-Kochanek K, Zheng Y, Geiger H (2012) Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell 10(5):520–530. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Forristal CE, Winkler IG, Nowlan B, Barbier V, Walkinshaw G, Levesque JP (2013) Pharmacologic stabilization of HIF-1alpha increases hematopoietic stem cell quiescence in vivo and accelerates blood recovery after severe irradiation. Blood 121(5):759–769. CrossRefPubMedGoogle Scholar
  36. Frisch BJ, Calvi LM (2014) Hematopoietic stem cell cultures and assays. Methods Mol Biol 1130:315–324. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Garcia TX, Hofmann MC (2015) Regulation of germ line stem cell homeostasis. Anim Reprod 12(1):35–45PubMedPubMedCentralGoogle Scholar
  38. Gassei K, Orwig KE (2016) Experimental methods to preserve male fertility and treat male factor infertility. Fertil Steril 105(2):256–266. CrossRefPubMedGoogle Scholar
  39. Geiger H, Koehler A, Gunzer M (2007) Stem cells, aging, niche, adhesion and Cdc42: a model for changes in cell-cell interactions and hematopoietic stem cell aging. Cell Cycle 6(8):884–887. CrossRefPubMedGoogle Scholar
  40. Giudice A, Caraglia M, Marra M, Montella M, Maurea N, Abbruzzese A, Arra C (2010) Circadian rhythms, adrenergic hormones and trafficking of hematopoietic stem cells. Expert Opin Ther Targets 14(5):567–575. CrossRefPubMedGoogle Scholar
  41. Grimaldi P, Di Giacomo D, Geremia R (2013) The endocannabinoid system and spermatogenesis. Front Endocrinol (Lausanne) 4:192. CrossRefGoogle Scholar
  42. Gurkan UA, Akkus O (2008) The mechanical environment of bone marrow: a review. Ann Biomed Eng 36(12):1978–1991. CrossRefPubMedGoogle Scholar
  43. Hai Y, Hou J, Liu Y, Liu Y, Yang H, Li Z, He Z (2014) The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and spermatogenesis. Semin Cell Dev Biol 29:66–75. CrossRefPubMedGoogle Scholar
  44. Hansel W (2010) The essentiality of the epididymal fat pad for spermatogenesis. Endocrinology 151(12):5565–5567. CrossRefPubMedGoogle Scholar
  45. Hoffman CM, Calvi LM (2014) Minireview: complexity of hematopoietic stem cell regulation in the bone marrow microenvironment. Mol Endocrinol 28(10):1592–1601. CrossRefPubMedPubMedCentralGoogle Scholar
  46. Horowitz MC, Berry R, Holtrup B, Sebo Z, Nelson T, Fretz JA, Lindskog D, Kaplan JL, Ables G, Rodeheffer MS, Rosen CJ (2017) Bone marrow adipocytes. Adipocytes 6(3):193–204. CrossRefGoogle Scholar
  47. Ieyasu A, Tajima Y, Shimba S, Nakauchi H, Yamazaki S (2014) Clock gene Bmal1 is dispensable for intrinsic properties of murine hematopoietic stem cells. J Negat Results Biomed 13:4. CrossRefPubMedPubMedCentralGoogle Scholar
  48. Ishige-Wada M, Kwon SM, Eguchi M, Hozumi K, Iwaguro H, Matsumoto T, Fukuda N, Mugishima H, Masuda H, Asahara T (2016) Jagged-1 signaling in the bone marrow microenvironment promotes endothelial progenitor cell expansion and commitment of CD133+ human cord blood cells for postnatal Vasculogenesis. PLoS One 11(11):e0166660. CrossRefPubMedPubMedCentralGoogle Scholar
  49. Itkin T, Gur-Cohen S, Spencer JA, Schajnovitz A, Ramasamy SK, Kusumbe AP, Ledergor G, Jung Y, Milo I, Poulos MG, Kalinkovich A, Ludin A, Kollet O, Shakhar G, Butler JM, Rafii S, Adams RH, Scadden DT, Lin CP, Lapidot T (2016) Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 532(7599):323–328. CrossRefPubMedGoogle Scholar
  50. Jalali AS (2017) Epididymal white adipose tissue: endocrine backbone of Spermatogonial stem cells maintenance. J Stem Cell Biol Transplant 1(3).
  51. Jankovic Velickovic L, Stefanovic V (2014) Hypoxia and spermatogenesis. Int Urol Nephrol 46(5):887–894. CrossRefPubMedGoogle Scholar
  52. Julien E, El Omar R, Tavian M (2016) Origin of the hematopoietic system in the human embryo. FEBS Lett 590(22):3987–4001. CrossRefPubMedGoogle Scholar
  53. Katayama Y, Battista M, Kao WM, Hidalgo A, Peired AJ, Thomas SA, Frenette PS (2006) Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124(2):407–421. CrossRefPubMedGoogle Scholar
  54. Kim J, Lee H, Selimović Š, Gauvin R, Bae H (2015) Organ-on-A-Chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow. Drug Saf 38(5):409–418. CrossRefPubMedGoogle Scholar
  55. Kirkpatrick CJ (2015) Modelling the regenerative niche: a major challenge in biomaterials research. Regen Biomater 2(4):267–272. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Klamer S, Voermans C (2014) The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone marrow microenvironment. Cell Adhes Migr 8(6):563–577. CrossRefGoogle Scholar
  57. Komeya M, Kimura H, Nakamura H, Yokonishi T, Sato T, Kojima K, Hayashi K, Katagiri K, Yamanaka H, Sanjo H, Yao M, Kamimura S, Inoue K, Ogonuki N, Ogura A, Fujii T, Ogawa T (2016) Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device. Sci Rep 6:21472. CrossRefPubMedPubMedCentralGoogle Scholar
  58. Komeya M, Hayashi K, Nakamura H, Yamanaka H, Sanjo H, Kojima K, Sato T, Yao M, Kimura H, Fujii T, Ogawa T (2017) Pumpless microfluidic system driven by hydrostatic pressure induces and maintains mouse spermatogenesis in vitro. Sci Rep 7(1):15459. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Köse S, Kaya FA, Denkbaş EB, Korkusuz P, Cetinkaya FD (2016) Evaluation of biocompatibility of random or aligned electrospun polyhydroxybutyrate scaffolds combined with human mesenchymal stem cells. Turk J Biol 40(2):410–419CrossRefGoogle Scholar
  60. Kose S, Aerts-Kaya F, Kopru CZ, Nemutlu E, Kuskonmaz B, Karaosmanoglu B, Taskiran EZ, Altun B, Uckan Cetinkaya D, Korkusuz P (2018) Human bone marrow mesenchymal stem cells secrete endocannabinoids that stimulate in vitro hematopoietic stem cell migration effectively comparable to beta-adrenergic stimulation. Exp Hematol 57:30–41 e31. CrossRefPubMedGoogle Scholar
  61. Kovtonyuk LV, Fritsch K, Feng X, Manz MG, Takizawa H (2016) Inflamm-aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment. Front Immunol 7:502. CrossRefPubMedPubMedCentralGoogle Scholar
  62. Kumar R, Godavarthy PS, Krause DS (2018) The bone marrow microenvironment in health and disease at a glance. J Cell Sci 131(4).
  63. Kurth I, Franke K, Pompe T, Bornhauser M, Werner C (2011) Extracellular matrix functionalized microcavities to control hematopoietic stem and progenitor cell fate. Macromol Biosci 11(6):739–747. CrossRefPubMedGoogle Scholar
  64. Kusumbe AP, Ramasamy SK, Itkin T, Mae MA, Langen UH, Betsholtz C, Lapidot T, Adams RH (2016) Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature 532(7599):380–384. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Landry D, Cloutier F, Martin LJ (2013) Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol 13(1):1–14. CrossRefPubMedGoogle Scholar
  66. Latchney SE, Calvi LM (2017) The aging hematopoietic stem cell niche: phenotypic and functional changes and mechanisms that contribute to hematopoietic aging. Semin Hematol 54(1):25–32. CrossRefPubMedGoogle Scholar
  67. Levesque JP, Helwani FM, Winkler IG (2010) The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia 24(12):1979–1992. CrossRefPubMedGoogle Scholar
  68. Levi F, Schibler U (2007) Circadian rhythms: mechanisms and therapeutic implications. Annu Rev Pharmacol Toxicol 47:593–628. CrossRefPubMedGoogle Scholar
  69. Li J, Carrillo Garcia C, Riedt T, Brandes M, Szczepanski S, Brossart P, Wagner W, Janzen V (2018) Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging. Sci Rep 8(1):2833. CrossRefPubMedPubMedCentralGoogle Scholar
  70. Lin S, Zhao R, Xiao Y, Li P (2015) Mechanisms determining the fate of hematopoietic stem cells. Stem Cell Investig 2:10. CrossRefPubMedPubMedCentralGoogle Scholar
  71. Lucas D (2017) The bone marrow microenvironment for hematopoietic stem cells. Adv Exp Med Biol 1041:5–18. CrossRefPubMedGoogle Scholar
  72. Ma JC, Huang X, Shen YW, Zheng C, Su QH, Xu JK, Zhao J (2016) Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen. Biosci Biotechnol Biochem 80(8):1470–1477. CrossRefPubMedGoogle Scholar
  73. Mamsen LS, Brochner CB, Byskov AG, Mollgard K (2012) The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge. Int J Dev Biol 56(10–12):771–778. CrossRefPubMedGoogle Scholar
  74. Mayerhofer A (2013) Human testicular peritubular cells: more than meets the eye. Reproduction 145(5):R107–R116. CrossRefPubMedGoogle Scholar
  75. Mei XX, Wang J, Wu J (2015) Extrinsic and intrinsic factors controlling spermatogonial stem cell self-renewal and differentiation. Asian J Androl 17(3):347–354. CrossRefPubMedPubMedCentralGoogle Scholar
  76. Meistrich ML, Shetty G (2015) The new director of “the Spermatogonial niche”: introducing the peritubular macrophage. Cell Rep 12(7):1069–1070. CrossRefPubMedGoogle Scholar
  77. Mendez-Ferrer S, Lucas D, Battista M, Frenette PS (2008) Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452(7186):442–447. CrossRefPubMedGoogle Scholar
  78. Mendez-Ferrer S, Chow A, Merad M, Frenette PS (2009) Circadian rhythms influence hematopoietic stem cells. Curr Opin Hematol 16(4):235–242. CrossRefPubMedPubMedCentralGoogle Scholar
  79. Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466(7308):829–834. CrossRefPubMedPubMedCentralGoogle Scholar
  80. Morrison SJ, Scadden DT (2014) The bone marrow niche for haematopoietic stem cells. Nature 505(7483):327–334. CrossRefPubMedPubMedCentralGoogle Scholar
  81. Muzes G, Sipos F (2016) Heterogeneity of stem cells: a brief overview. Methods Mol Biol 1516:1–12. CrossRefPubMedGoogle Scholar
  82. Nakamura-Ishizu A, Takubo K, Kobayashi H, Suzuki-Inoue K, Suda T (2015) CLEC-2 in megakaryocytes is critical for maintenance of hematopoietic stem cells in the bone marrow. J Exp Med 212(12):2133–2146. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ (2009) Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 460(7252):259–263. CrossRefPubMedPubMedCentralGoogle Scholar
  84. Nombela-Arrieta C, Pivarnik G, Winkel B, Canty KJ, Harley B, Mahoney JE, Park SY, Lu J, Protopopov A, Silberstein LE (2013) Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nat Cell Biol 15(5):533–543. CrossRefPubMedPubMedCentralGoogle Scholar
  85. Omatsu Y, Nagasawa T (2015) The critical and specific transcriptional regulator of the microenvironmental niche for hematopoietic stem and progenitor cells. Curr Opin Hematol 22(4):330–336. CrossRefPubMedGoogle Scholar
  86. Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N, Kohno K, Nagasawa T (2010) The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 33(3):387–399. CrossRefPubMedGoogle Scholar
  87. Patel VS, Ete Chan M, Rubin J, Rubin CT (2018) Marrow adiposity and hematopoiesis in aging and obesity: exercise as an intervention. Curr Osteoporos Rep 16(2):105–115. CrossRefPubMedGoogle Scholar
  88. Potter SJ, DeFalco T (2017) Role of the testis interstitial compartment in spermatogonial stem cell function. Reproduction 153(4):R151–R162. CrossRefPubMedPubMedCentralGoogle Scholar
  89. Rafii S, Shapiro F, Pettengell R, Ferris B, Nachman RL, Moore MA, Asch AS (1995) Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors. Blood 86(9):3353–3363PubMedGoogle Scholar
  90. Redondo PA, Pavlou M, Loizidou M, Cheema U (2017) Elements of the niche for adult stem cell expansion. J Tissue Eng 8:2041731417725464. CrossRefPubMedPubMedCentralGoogle Scholar
  91. Rossi P, Dolci S (2013) Paracrine mechanisms involved in the control of early stages of mammalian spermatogenesis. Front Endocrinol (Lausanne) 4:181. CrossRefGoogle Scholar
  92. Rossi SP, Walenta L, Rey-Ares V, Kohn FM, Schwarzer JU, Welter H, Calandra RS, Frungieri MB, Mayerhofer A (2018) Alpha 1 adrenergic receptor-mediated inflammatory responses in human testicular peritubular cells. Mol Cell Endocrinol.
  93. Saez B, Ferraro F, Yusuf RZ, Cook CM, Yu VW, Pardo-Saganta A, Sykes SM, Palchaudhuri R, Schajnovitz A, Lotinun S, Lymperi S, Mendez-Ferrer S, Toro RD, Day R, Vasic R, Acharya SS, Baron R, Lin CP, Yamaguchi Y, Wagers AJ, Scadden DT (2014) Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning. Blood 124(19):2937–2947. CrossRefPubMedPubMedCentralGoogle Scholar
  94. Sagar BM, Rentala S, Gopal PN, Sharma S, Mukhopadhyay A (2006) Fibronectin and laminin enhance engraftibility of cultured hematopoietic stem cells. Biochem Biophys Res Commun 350(4):1000–1005. CrossRefPubMedGoogle Scholar
  95. Sargent KM, Clopton DT, Lu N, Pohlmeier WE, Cupp AS (2016) VEGFA splicing: divergent isoforms regulate spermatogonial stem cell maintenance. Cell Tissue Res 363(1):31–45. CrossRefPubMedGoogle Scholar
  96. Sarkaria SM, Decker M, Ding L (2018) Bone marrow micro-environment in normal and deranged hematopoiesis: opportunities for regenerative medicine and therapies. BioEssays 40(3).
  97. Scheller EL, Cawthorn WP, Burr AA, Horowitz MC, MacDougald OA (2016) Marrow adipose tissue: trimming the fat. Trends Endocrinol Metab 27(6):392–403. CrossRefPubMedPubMedCentralGoogle Scholar
  98. Schofield R (1978) The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4(1–2):7–25PubMedGoogle Scholar
  99. Schrade A, Kyronlahti A, Akinrinade O, Pihlajoki M, Fischer S, Rodriguez VM, Otte K, Velagapudi V, Toppari J, Wilson DB, Heikinheimo M (2016) GATA4 regulates blood-testis barrier function and lactate metabolism in mouse Sertoli cells. Endocrinology 157(6):2416–2431. CrossRefPubMedPubMedCentralGoogle Scholar
  100. Shiraishi K, Matsuyama H (2017) Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]. Endocr J 64(2):123–131. CrossRefPubMedGoogle Scholar
  101. Song HW, Wilkinson MF (2014) Transcriptional control of spermatogonial maintenance and differentiation. Semin Cell Dev Biol 30:14–26. CrossRefPubMedGoogle Scholar
  102. Spindler TJ, Tseng AW, Zhou X, Adams GB (2014) Adipocytic cells augment the support of primitive hematopoietic cells in vitro but have no effect in the bone marrow niche under homeostatic conditions. Stem Cells Dev 23(4):434–441. CrossRefPubMedGoogle Scholar
  103. Suchacki KJ, Cawthorn WP, Rosen CJ (2016) Bone marrow adipose tissue: formation, function and regulation. Curr Opin Pharmacol 28:50–56. CrossRefPubMedPubMedCentralGoogle Scholar
  104. Sugimura R (2016) Bioengineering hematopoietic stem cell niche toward regenerative medicine. Adv Drug Deliv Rev 99((Pt B)):212–220. CrossRefPubMedGoogle Scholar
  105. Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25(6):977–988. CrossRefPubMedGoogle Scholar
  106. Taichman RS, Reilly MJ, Emerson SG (1996) Human osteoblasts support human hematopoietic progenitor cells in vitro bone marrow cultures. Blood 87(2):518–524PubMedGoogle Scholar
  107. Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, Shima H, Johnson RS, Hirao A, Suematsu M, Suda T (2010) Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7(3):391–402. CrossRefPubMedGoogle Scholar
  108. Tuljapurkar SR, McGuire TR, Brusnahan SK, Jackson JD, Garvin KL, Kessinger MA, Lane JT, BJ OK, Sharp JG (2011) Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging. J Anat 219(5):574–581. CrossRefPubMedPubMedCentralGoogle Scholar
  109. van den Driesche S, Sharpe RM, Saunders PT, Mitchell RT (2014) Regulation of the germ stem cell niche as the foundation for adult spermatogenesis: a role for miRNAs? Semin Cell Dev Biol 29:76–83. CrossRefPubMedGoogle Scholar
  110. Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert SR, Bouxsein ML, Faugere MC, Guldberg RE, Gerstenfeld LC, Haase VH, Johnson RS, Schipani E, Clemens TL (2007) The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 117(6):1616–1626. CrossRefPubMedPubMedCentralGoogle Scholar
  111. Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F, Poulton IJ, van Rooijen N, Alexander KA, Raggatt LJ, Levesque JP (2010) Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 116(23):4815–4828. CrossRefPubMedGoogle Scholar
  112. Winkler IG, Barbier V, Nowlan B, Jacobsen RN, Forristal CE, Patton JT, Magnani JL, Levesque JP (2012) Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat Med 18(11):1651–1657. CrossRefPubMedGoogle Scholar
  113. Xing Z, Ryan MA, Daria D, Nattamai KJ, Van Zant G, Wang L, Zheng Y, Geiger H (2006) Increased hematopoietic stem cell mobilization in aged mice. Blood 108(7):2190–2197. CrossRefPubMedPubMedCentralGoogle Scholar
  114. Yadegar M, Hekmatimoghaddam SH, Nezami Saridar S, Jebali A (2015) The viability of mouse spermatogonial germ cells on a novel scaffold, containing human serum albumin and calcium phosphate nanoparticles. Iran J Reprod Med 13(3):141–148PubMedPubMedCentralGoogle Scholar
  115. Yang QE, Kim D, Kaucher A, Oatley MJ, Oatley JM (2013) CXCL12-CXCR4 signaling is required for the maintenance of mouse spermatogonial stem cells. J Cell Sci 126(Pt 4):1009–1020. CrossRefPubMedPubMedCentralGoogle Scholar
  116. Yin X, Mead BE, Safaee H, Langer R, Karp JM, Levy O (2016) Engineering stem cell organoids. Cell Stem Cell 18(1):25–38. CrossRefPubMedPubMedCentralGoogle Scholar
  117. Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M, Strauss-Ayali D, Viukov S, Guilliams M, Misharin A, Hume DA, Perlman H, Malissen B, Zelzer E, Jung S (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38(1):79–91. CrossRefPubMedGoogle Scholar
  118. Yu Y, Alkhawaji A, Ding Y, Mei J (2016) Decellularized scaffolds in regenerative medicine. Oncotarget 7(36):58671–58683. CrossRefPubMedPubMedCentralGoogle Scholar
  119. Zhang H, Yin Y, Wang G, Liu Z, Liu L, Sun F (2014) Interleukin-6 disrupts blood-testis barrier through inhibiting protein degradation or activating phosphorylated ERK in Sertoli cells. Sci Rep 4:4260. CrossRefPubMedPubMedCentralGoogle Scholar
  120. Zhao M, Perry JM, Marshall H, Venkatraman A, Qian P, He XC, Ahamed J, Li L (2014) Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells. Nat Med 20(11):1321–1326. CrossRefPubMedGoogle Scholar
  121. Zhou Y, Tsai TL, Li WJ (2017) Strategies to retain properties of bone marrow-derived mesenchymal stem cells ex vivo. Ann N Y Acad Sci 1409(1):3–17. CrossRefPubMedPubMedCentralGoogle Scholar
  122. Zhu RJ, Wu MQ, Li ZJ, Zhang Y, Liu KY (2013) Hematopoietic recovery following chemotherapy is improved by BADGE-induced inhibition of adipogenesis. Int J Hematol 97(1):58–72. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Sevil Köse
    • 1
  • Nilgün Yersal
    • 2
  • Selin Önen
    • 3
  • Petek Korkusuz
    • 2
    Email author
  1. 1.Faculty of Health Sciences, Department of Nutrition and DieteticsAtilim UniversityAnkaraTurkey
  2. 2.Faculty of Medicine, Department of Histology and EmbryologyHacettepe UniversityAnkaraTurkey
  3. 3.Department of Stem Cell Sciences, Institute of Health SciencesHacettepe UniversityAnkaraTurkey

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