Regulation of haemopoiesis in long-term bone marrow cultures. IV. Glycosaminoglycan synthesis and the stimulation of haemopoiesis by beta-D-xylosides.

Abstract

Sulfated glycosaminoglycans (GAGs) are distributed in consistent and distinctive patterns between the cell surface and the growth medium of haemopoietically active longterm bone marrow cultures. Heparan sulfate is the main cell surface component and chondroitin sulfate is the major sulfated species in the medium. When the cultures are supplemented with /Y-D-xylosides a significant increase in chondroitin sulfate synthesis is observed but no stimulation of heparan sulfate synthesis occurs. The chondroitin sulfate accumulates in the culture medium in/~-D-xyloside-treated cultures but the composition of sulfated GAGs in cellsurface derived material is unaffected. ,8-D-xylosides also stimulate the production of haemopoietic cells without any apparent alteration in the adherent stromal cells of the marrow cultures. Equivalent increases are obtained in cells at all stages of development so that a fivefold increase in pluripotent stem cells (CFU-S) is matched by fivefold increase in the granulocyte-macrophage progenitors (GM-CFC) and in mature granulocytes. The stimulation persists for many weeks in fl-D-xyloside-treated cultures. These results indicate that the sulfated GAGs may play an important role in the regulation of haemopoiesis.

Inhibition of collagen deposition in the extracellular matrix prevents the establishment of a stroma supportive of hematopoiesis in long-term murine bone marrow cultures.

“…The hemopoietic microenvironment is acknowledged widely to be essential for maintenance and differentiation of hemopoietic progenitor cells in vivo (1, 2) and in vitro (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Although the cellular composition of the hemopoietic microenvironment has been studied extensively, the composition of the extracellular matrix has been defined only partially.…”

“…The long-term murine bone marrow cell culture system, which in many ways appears to parallel hemopoiesis in vivo, is a useful and convenient means of studying the role of the microenvironment in supporting hematopoiesis (3)(4)(5)(6)(7)(8). Long-term hematopoiesis is initiated and sustained in these cultures only after the establishment on the surface of the culture vessel of an adherent stromal cell layer consisting of macrophages, endothelial cells, adventitial reticular cells, fibroblasts, adipocytes, and perhaps other unidentified cells (3)(4)(5)(6)(7)(8), as well as an extracellular matrix (ECM)' consisting of collagen, fibronectin, laminin, proteoglycans, and probably other unidentified components (8)(9)(10)(11)(12). The purpose of this report is to define the role of extracellular collagen in the maintenance of long-term hematopoiesis in vitro.…”

Maintenance of CD34 Expression During Proliferation of CD34 + Cord Blood Cells on Glycosaminoglycan Surfaces

“…A number of studies have indicated that glycosaminoglycans bind and present cytokines to hematopoietic cells in a more highly active form [6,7,9,[12][13][14]. Most notably, the results show that heparan sulfate is required for maintenance of long-term culture-initiating cells (LTC-ICs) [9].…”

Skeletogenesis and the Hematopoietic Niche

“…On the other hand, cell-matrix interactions influence not only cell behavior, but also cell anchorage to the niche. To date, the matrix proteins within the HME include: collagens (Types I, II, III, IV and X), glycoproteins (fibronectin, lamanin, nidogen, tenasin C, thrombospondin, vitronectin), PGs (perlecan, decorin, agrin) and the GAG hyaluronan (Bentley and Foidart 1980;Bentley 1982;Spooncer et al 1983;Zuckerman and Wicha 1983;Zuckerman et al 1985;Klein 1995;Ohta et al 1998;Campbell et al 2004;Mazzon et al 2011). These matrix constituents can signal to hematopoietic cells through cell receptors such as: integrins, immunoglobulin-like molecules, cadherins, selectins, and mucins (Teixido et al 1992;Coulombel et al 1997;Levesque and Simmons 1999;Zhang, J. et al 2003;Merzaban et al 2011).…”