PMID: 16533727Mar 15, 2006Paper

The effects of glycosaminoglycans on thrombopoietin-induced megakaryocytopoiesis

Haematologica
Ikuo KashiwakuraKeiichi Takagaki

Abstract

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 CD34+ megakaryocytic progenitor cells (CFU-Meg) were evaluated in vitro. CD34+ cells were highly purified from steady-state human peripheral blood. The GAG tested were hyaluronic acid (from humans, pigs and roosters), keratan sulfate, heparan sulfate, chondroitin sulfate (from whale, shark or squid cartilage) and dermatan sulfate (DS). When used alone, none of the GAG supported the clonal growth of CFU-Meg; however, in cultures stimulated by recombinant human thrombopoietin, human hyaluronic acid, whale chondroitin sulfate 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 thrombopoietin alone after 9-12 days of serum-free liquid culture. Furthermore, DS induced the generation of hyperploid megakaryocytes and promoted pro-platelet formation. Chemical fragmentation and desulfation of DS s...Continue Reading

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