Abstract

Bone marrow is a specialized site of structural stromal cells of immature and mature blood cells. It is found in bones such as the human skull, rib cage, ribs, pelvis and femur. Bone marrow is connected to the invention and circulation through specialized blood vessels, including specialized fenestrated capillaries called sinusoids. These sinusoids penetrate sponge-like extracellular cells which is produced by fibroblasts, and place hematopoietic cells, proteins in separate compartments. Bone marrow contains specialized microchips containing hematopoietic cells, stromal cells, ECM, cytokines, growth factors and chemokines. In this microenvironment, developing hematopoietic cells are signaling for survival, differentiation and proliferation. Bone marrow microenvironment plays an important role in the development and progression of leukemia and other types of cancer. In many ways, bone marrow provides an ideal microenvironment for growth of malignant cells. In this review, general information about the role of the bone marrow microenvironment and the cells forming the microenvironment is given

Keywords

• Bone marrow, Hematopoietic stem cell, Mesenchymal stem cell, Microenvironment

Kemik İliği Stroması: Hücreleri ve Mikroçevresi

Abstract

Kemik iliği olgunlaşmamış ve olgunlaşmış kan hücrelerinin yapısal stromal hücrelerle kapatıldığı özel bir yerdir. Bu süngerimsi yağ dokusu, insan kafatası, göğüs kafesi, kaburgalar, pelvis ve femurlar gibi kemiklerin içinde bulunur. Kemik iliği, sinüzoid olarak adlandırılan özelleştirilmiş fenestra kapiller dahil olmak üzere, uzmanlaşmış kan damarları aracılığıyla beslenir ve dolaşıma bağlanır. Bu sinüzoidler retiküler fibroblastlar tarafından üretilen sünger benzeri hücre dışı matrise (ECM) nüfuz eder ve bu hücreler ve proteinler, hematopoietik hücreleri ayrı bölmelere yerleştirir. Kemik iliğinde, hematopoietik hücreler, stromal hücreler, ECM, sitokinler, büyüme faktörleri ve kemokinler ihtiva eden özel mikroçevreler bulunur. Bu mikroçevrede gelişmekte olan hematopoietik hücreler hayatta kalmak, farklılaşmak ve çoğalmak için sinyal alırlar. Kemik iliği mikroçevresi löseminin ve diğer kanser türlerinin gelişiminde ve ilerlemesinde önemli bir rol oynamaktadır. Birçok yönden, kemik iliği malign hücrelerin büyümesi için ideal bir mikroçevre sağlamaktadır. Bu derlemede, kemik iliği mikroçevresinin görevi ve mikroçevreyi oluşturan hücrelerin hakkında genel bilgi verilmiştir

Keywords

• Kemik iliği, Hematopoetik kök hücre, Mezenkimal kök hücre, Mikroçevre

References

1. ABBOUD, C.N. AND LİCHTMAN, M.A. (2006). Structure of the marrow and the hematopoietic microenvironment, in Williams Hematology, 7th edn (eds M.A. Lichtman, E. Beutler, T.J. Kipps et al.), McGraw-Hill, New York, pp. 45–52.
2. ADAMS, G.B., CHABNER, K.T., ALLEY, I.R., OLSON, D.P., SZCZEPİORKOWSKİ, Z.M., POZNANSKY, M.C., KOS, C.H., POLLAK, M.R., BROWN, E.M., SCADDEN, D.T. (2006). Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature. 439:599–603.
3. ARAI, F., HİRAO, A., OHMURA, M., SATO, H., MATSUOKA, S, TAKUBO K, ITO K, KOH GY, SUDA T. (2004). Tie2/ angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell.; 118:149–161.
4. AVRAHAM, H., SCADDEN, D.T., CHİ, S. ET AL. (1992) Interaction of human bone marrow fibroblasts with megakaryocytes: role of the c-kit ligand. Blood, 80, 1679–1684.
5. BAINTON, D.F., MALONEY, M.A., PATT, H.M., AND STERN, R. (1986) Characterization of rabbit stromal fibroblasts derived from red and yellow bone marrow. Journal of Experimental Medicine, 163, 400–413.
6. BALKWILL, F. AND MANTOVANİ, A. (2001) Inflammation and cancer: back to Virchow? Lancet, 357, 539–545.
7. BELAID-CHOUCAIR, Z., LEPELLETIER, Y., PONCIN, G. ET AL. (2008) Human bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition. Stem Cells, 26, 1556–1564.
8. BIANCO, P., ROBEY, P.G., AND SIMMONS, P.J. (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell, 2, 313–319.

9. BLAIR, P. AND FLAUMENHAFT, R. (2009) Platelet alpha-granules: basic biology and clinical correlates. Blood Reviews, 23, 177–189.
10. BORD, S., BEAVAN, S., IRELAND, D. ET AL. (2001) Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: role of locally produced growth factors. Bone, 29, 216–222.
11. BROXMEYER, H.E., ORSCHELL, C.M., CLAPP, D.W. ET AL. (2005) Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. Journal of Experimental Medicine, 201, 1307–1318.
12. CALVI, L.M., ADAMS, G.B., WEIBRECHT, K.W., WEBER, J.M., OLSON, D.P., KNIGHT, M.C., MARTIN, R.P., SCHIPANI, E., DİVIETI, P., BRİNGHURST, F.R., MILNER, L.A., KRONENBERG, H.M., SCADDEN, D.T. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425:841–846.
13. CORRE, J., BARREAU, C., COUSİN, B. (2006) Human subcutaneous adipose cells support complete differentiation but not self-renewal of hematopoietic progenitors. Journal of Cellular Physiology, 208, 282–288.
14. DAR, A., GOİCHBERG, P., SHİNDER, V. ET AL. (2005) Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nature Immunology, 6, 1038–1046.
15. DENNIS, J.E. AND CHARBORD, P. (2002). Origin and differentiation of human and murine stroma. Stem Cells, 20, 205–214.
16. DEVINE, S.M., BARTHOLOMEW, A.M., MAHMUD, N. ET AL. (2001). Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. Experimental Hematology, 29, 244–255.
17. DIMASCIO, L., VOERMANS, C., UQOEZWA, M. ET AL. (2007). Identification of adiponectin as a novel hemopoietic stem cell growth factor. Journal of Immunology, 178, 3511–3520.
18. DIPPOLITO, G., DIABIRA, S., HOWARD, G.A. ET AL. (2004). Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. Journal of Cell Science, 117, 2971 – 2981.
19. FIBBE, W.E., VAN DAMME, J., BILLIAU, A. ET AL. (1988). Human fibroblasts produce granulocyte-CSF, macrophage-CSF, and granulocytemacrophage-CSF following stimu- lation by interleukin-1 and poly(rI). poly(rC). Blood, 72, 860–866.
20. GUBA, S.C., SARTOR, C.I., GOTTSCHALK, L.R. ET AL. (1992). Bone marrow stromal fibrob- lasts secrete interleukin-6 and granulocytemacrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme- linked immunosorbent assay, and reverse transcriptase polymerase chain reaction. Blood, 80, 1190–1198.
21. GUERRIERO, A., WORFORD, L., HOLLAND, H.K. ET AL. (1997). Thrombopoietin is synthesized by bone marrow stromal cells. Blood, 90, 3444–3455.
22. GUPTA, P., OEGEMA, T.R. JR., BRAZİL, J.J., ET AL. (1998). Structurally specific heparan sulfates support primitive human hematopoiesis by formation of a multimolecular stem cell niche. Blood, 92, 4641–4651.
23. IWASAKI H, SUDA T. (2009). Cancer stem cells and their niche. Cancer Science. 100:1166–1172. KACENA, M.A., GUNDBERG, C.M., AND HOROWİTZ, M.C. (2006) A reciprocal regulatory inter- action between megakaryocytes, bone cells, and hematopoietic stem cells. Bone, 39, 978 – 984. KARTSOGIANNIS, V., ZHOU, H., HORWOOD, N.J. ET AL. (1999) Localization of RANKL (receptor activator of NF kappa B ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone, 25, 525–534.
24. KAUSHANSKY, K., LIN, N., AND ADAMSON, J.W. (1988) Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors. Mechanism for the hematopoietic response to inflammation. Journal of Clinical Investigation, 81, 92–97.
25. KIEL, M.J., MORRİSON, S.J. (2008). Uncertainty in the niches that maintain haematopoietic stem cells. Nat Rev Immunol 8: 290-301.
26. KREIS, T. AND VALE, R. (1999). Extracellular Matrix, Anchor, and Adhesion Proteins, Oxford University Press, Inc., New York.
27. KUZNETSOV, S.A., MANKANI, M.H., GRONTHOS, S. et al. (2001). Circulating skeletal stem cells. Journal of Cell Biology, 153, 1133–1140.
28. LAMAGNA, C., AURRAND-LIONS, M., AND IMHOF, B.A. (2006). Dual role of macrophages in tumor growth and angiogenesis. Journal of Leukocyte Biology, 80, 705–713.
29. LINK, D.C. (2000). Mechanisms of granulocyte colony-stimulating factor-induced hematopoi- etic progenitor-cell mobilization. Seminars in Hematology, 37, 25–32.
30. MACKIE, E.J. (2003). Osteoblasts: novel roles in orchestration of skeletal architecture. International Journal of Biochemistry and Cell Biology, 35, 1301–1305.
31. MIHARADA, K., HIROYAMA, T., SUDO, K. ET AL. (2008). Lipocalin 2-mediated growth suppression is evident in human erythroid and monocyte/macrophage lineage cells. Journal of Cellular Physiology, 215, 526–537.
32. MOORE, K.A. AND LEMİSCHKA, I.R. (2006). Stem cells and their niches. Science, 311, 1880 – 1885. MURUGANANDAN, S., ROMAN, A.A., AND SİNAL, C.J. (2009). Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program. Cellular and Molecular Life Science, 66, 236–253.
33. NUTTALL, M.E. AND GIMBLE, J.M. (2004). Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Current Opinion in Pharmacology, 4, 290–294.
34. PANG, L., WEİSS, M.J., AND PONCZ, M. (2005). Megakaryocyte biology and related disorders. Journal of Clinical Investigation, 115, 3332–3338.
35. PERRY, J.M., LI, L. (2007). Disrupting the stem cell niche: good seeds in bad soil. Cell.; 129:1045- 1047. PITTENGER, M.F., MACKAY, A.M., BECK, S.C. ET AL. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147.
36. PORTER, R.L. AND CALVI, L.M. (2008). Communications between bone cells and hematopoietic stem cells. Archives of Biochemistry and Biophysics, 473, 193–200.
37. PROCKOP, D.J. (1997). Marrow stromal cells as stem cells for nonhematopoietic tissues. Science, 276, 71–74.
38. RAFII, S., MOHLE, R., SHAPIRO, F. ET AL. (1997). Regulation of hematopoiesis by microvascular endothelium. Leukemia and Lymphoma, 27, 375–386.
39. REDDY, S.V. AND ROODMAN, G.D. (1998). Control of osteoclast differentiation. Critical Reviews in Eukaryotic Gene Expression, 8, 1–17.
40. REYES, M., LUND, T., LENVIK, T. ET AL. (2001). Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood, 98, 2615–2625.
41. RIBATTI, D., NICO, B., CRIVELLATO, E., AND VACCA, A. (2007) Macrophages and tumor angiogen- esis. Leukemia, 21, 2085–2089.
42. ROODMAN, G.D. (1999) Cell biology of the osteoclast. Experimental Hematology, 27, 1229 – 1241. SACCHETTI, B., FUNARİ, A., MİCHİENZİ, S. ET AL. (2007). Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell, 131, 324–336.
43. SCHMİTT, M., SCHMITT, A., ROJEWSKİ, M.T. ET AL. (2008). RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood, 111, 1357–1365.
44. SCHRODER HC, WANG XH, WIENS M, DIEHL-SEIFERT B, KROPF K, SCHLOßMACHER U, MÜLLER WE. (2012). Silicate modulates the cross-talk between osteoblasts (SaOS-2) and osteoclasts (RAW 264.7 cells): inhibition of osteoclast growth and differentiation. Journal of Cellular Biochemistry; 113:3197–3206.
45. SHIH, I.M. (1999) The role of CD146 (Mel-CAM) in biology and pathology. Journal of Pathology, 189, 4–11.
46. SHIOZAWA, Y., HAVENS, A.M., PIENTA, K.J., AND TAICHMAN, R.S. (2008) The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites. Leukemia, 22, 941–950.
47. SIPE, J.B., ZHANG, J., WAITS, C. ET AL. (2004) Localization of bone morphogenetic proteins (BMPs)-2, -4, and -6 within megakaryocytes and platelets. Bone, 35, 1316–1322.
48. STEURER, M., KERN, J., ZİTT, M. ET AL. (2008) Quantification of circulating endothelial and progenitor cells: comparison of quantitative PCR and four-channel flow cytometry. BMC Research Notes, 1, 71.
49. TABE, Y., KONOPLEVA, M., (2014). Advances In Understanding The Leukemia Microenvironment Br J Haematol. March; 164(6): 767–778.
50. TAICHMAN, R.S. AND EMERSON, S.G. (1998) The role of osteoblasts in the hematopoietic microenvironment. Stem Cells, 16, 7–15.
51. THIELE, J. AND KVASNİCKA, H.M. (2007) Myelofibrosis what’s in a name? Consensus on definition and EUMNET grading. Pathobiology, 74, 89–96.
52. UNTERGASSER, G., KOECK, R., WOLF, D. ET AL. (2006) CD34+/CD133- circulating endothelial precursor cells (CEP): characterization, senescence and in vivo application. Experimental Gerontology, 41, 600–608.
53. YAN, Q.W., YANG, Q., MODY, N. ET AL. (2007) The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes, 56, 2533–254.