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Effect of immobilized glycosaminoglycans on megakaryocyte expansion, apoptosis and platelet release
Author(s) -
Kishore Vipuil,
Eliason James F.,
Matthew Howard W.T.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.522.6
Subject(s) - glycosaminoglycan , chemistry , apoptosis , megakaryocyte , platelet , flow cytometry , haematopoiesis , heparan sulfate , dermatan sulfate , in vitro , microbiology and biotechnology , thrombopoiesis , transplantation , platelet activation , andrology , immunology , stem cell , biology , biochemistry , medicine
Umbilical cord blood transplantation in adults is limited due to delayed platelet recovery. Transfusion of expanded megakaryocytes (MKs) derived from hematopoietic stem cells (HSCs) has been suggested as a potential solution. Glycosaminoglycans (GAGs) have been shown to influence the proliferation and differentiation of HSCs. Our objective in this study was to examine the effects of various immobilized GAGs on the expansion, apoptosis, ploidy, and platelet release of CD41+ MK progenitors in vitro. Cultures were conducted in serum free media supplemented with TPO. Freshly isolated HSC were seeded onto 24 well plates coated with GAG‐derivatized chitosan membranes. Controls consisted of plastic and un‐derivatized chitosan membranes. Wells were demidepopulated at intervals and analyzed by flow cytometry. At day 11, GAG surfaces like heparin, dermatan sulfate, hyaluronan and heparan sulfate showed significantly lower (p < 0.05) MK apoptotic fractions compared to plastic. The apoptotic MK fraction on GAG surfaces increased with time and was comparable to plastic by day 17. However, the reduced early apoptosis resulted in overall higher MK proliferation on GAGs. MKs on all surfaces had a ploidy level below 8N. On all surfaces, platelet numbers correlated closely with the number of apoptotic MKs at all time points. Results show that GAG surfaces may be useful tools to enhance in vitro production of MKs. NIH Supported.