Bone marrow stromal proteoglycans regulate megakaryocytic differentiation of human progenitor cells

Experimental Cell Research
S ZweegmanA M Dräger

Abstract

Adherence of hematopoietic progenitor cells (HPCs) to stroma is an important regulatory step in megakaryocytic differentiation. However, the mechanisms through which megakaryocytic progenitors are inhibited by stroma are poorly understood. We examined the role of sulfated glycoconjugates, such as proteoglycans (PGs), on human bone marrow stroma (hBMS). To this end, PG structure was altered by desulfation or enzymatic cleavage. PGs participated in adhesion of human HPC, as desulfation resulted in about 50% decline in adhesion to hBMS. Heparan sulfate proteoglycans (HSPGs) were found to be responsible by showing about 25% decline in adhesion after pre-incubation of HPC with heparin and about 15% decline in adhesion after enzymatic removal of HSPGs from hBMS. Furthermore, PGs were involved in binding cytokines. Both desulfation and enzymatic removal of stromal HSPGs increased release of megakaryocytopoiesis-inhibiting cytokines, that is, interleukin-8 (IL-8, 1.9-fold increase) and macrophage inflammatory protein-1alpha (MIP-1alpha, 1.4-fold increase). The megakaryocytic output of HPC grown in conditioned medium of desulfated stroma was decreased to 50% of the megakaryocytic output in CM of sulfated stroma. From these studies, it c...Continue Reading

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Citations

Nov 18, 2008·Experimental Hematology·Brent SullenbargerLarry C Lasky
Jun 13, 2006·Journal of Cellular Biochemistry·Simon M Cool, Victor Nurcombe
May 25, 2007·Matrix Biology : Journal of the International Society for Matrix Biology·Sonja ZweegmanJacob van den Born
Jun 12, 2020·Platelets·Vittorio AbbonanteAlessandra Balduini
Jan 9, 2010·Journal of Radiation Research·Naoki HayashiIkuo Kashiwakura
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Maanasa RavikumarSimon M Cool

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