BACKGROUND AND OBJECTIVES: The extracellular matrix plays an essential role in normal hematopoiesis. Proteoglycans and glycosaminoglycans (GAG) are major components of the matrix. In this study, the effects of various GAG on the proliferation and differentiation of @entity2280 + megakaryocytic progenitor cells (CFU-Meg) were evaluated in vitro. DESIGN AND METHODS: @entity2280 + cells were highly purified from steady-state @entity1 peripheral blood. The GAG tested were hyaluronic acid (from @entity1 , @entity1707 and roosters), keratan @entity597 , @entity31847 , chondroitin @entity597 (from whale, shark or squid cartilage) and dermatan @entity597 (DS). RESULTS: When used alone, none of the GAG supported the clonal growth of CFU-Meg; however, in cultures stimulated by recombinant @entity1 @entity21929 , @entity1 hyaluronic acid, whale @entity12006 and DS significantly enhanced such growth. In particular, the addition of DS resulted in increases of about 1.3-fold, 1.6-fold and 2.0-fold in the numbers of total cells, megakaryocytes and CFU-Meg, respectively, compared with the control culture stimulated by @entity21929 alone after 9-12 days of serum-free liquid culture. Furthermore, DS induced the generation of hyperploid megakaryocytes and promoted pro-platelet formation. @entity1949 and desulfation of DS showed that a chain of at least 12 saccharides is required for colony-promoting activity and that the @entity597 groups play an essential role. INTERPRETATION AND CONCLUSIONS: DS acts on an immature population of @entity2280 + cells, stimulates the proliferation of CFU-Meg, and enhances the terminal maturation of megakaryocytes and thrombopoiesis. These results suggest that DS has a wide spectrum of action in promoting megakaryocytopoiesis and thrombopoiesis.

The effects of glycosaminoglycans on XXXX -induced megakaryocytopoiesis.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity1707 :: ('9823', 'Species') :: ['pigs'] @entity21929 :: ('MESH:D013926', 'Chemical') :: ['thrombopoietin'] @entity1949 :: ('MESH:D012892', 'Disease') :: ['Chemical fragmentation'] @entity31847 :: ('MESH:D006497', 'Chemical') :: ['heparan sulfate'] @entity12006 :: ('MESH:D002809', 'Chemical') :: ['chondroitin sulfate'] @entity2280 :: ('947', 'Gene') :: ['CD34'] @entity597 :: ('CHEBI:16189', 'Chemical') :: ['sulfate']
@entity21929 :: (MESH:D013926,Chemical) :: ['thrombopoietin']
