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Formation of an adherent hematopoietic expansion culture using fucoidan
journal contribution
posted on 2023-05-17, 11:49 authored by Irhimeh, MR, Fitton, JH, Ko, K, Raymond Lowenthal, Nordon, REExpansion of transplantable cord blood (CB) progenitors using a stroma requires provision of an exogenous cell source because of the low frequency of stromal precursor cells in CB. A simpler approach from a clinical regulatory perspective would be to provide synthetic extracellular matrix. The aim of this study was to characterize the effect on hematopoietic cell culture of fucoidan. The modulation of cytokine-driven hematopoietic cell expansion by fucoidan was investigated using two-level fractional and full factorial experimental designs. Mobilized peripheral blood (PB) CD34+ cells were grown over 10 days in various combinations of FL, SCF, TPO, G-CSF, and SDF-1. Cultures were analyzed by immunophenotype. The effect of fucoidan on the divisional recruitment of CD34+ cells was studied by CFDA-SE division tracking. Fucoidan was adsorbed by polystyrene to tissue culture plates and promoted formation of an adherent hematopoietic culture. Factorial design experiments with mobilized PB-CD34+cells showed that fucoidan reduced the production of CD34+ cells and CD34+CXCR4+ ratio but did not affect the production of monocytic, granulocytic, or megakaryocytic cells. The inhibitory effect of fucoidan on expansion of CB-CD34+ cells was greater than mobilized PB. Division tracking analysis showed that CD34+ cell generation times were lengthened by fucoidan. Fucoidan binds growth factors via their heparin-binding domain. The formation of an adherent hematopoietic culture system by fucoidan is most likely mediated by the binding of L-selectin and integrin-αMβ2 on myeloids. Fucoidan deserves further investigation as glycan scaffold that is suitable for immobilization of other matrix molecules thought to comprise blood stem cell niche.
History
Publication title
Annals of HematologyVolume
90Issue
9Pagination
1005-1015ISSN
0939-5555Department/School
Tasmanian School of MedicinePublisher
SpringerPlace of publication
HeidelbergRights statement
Copyright 2011 Springer-VerlagRepository Status
- Restricted