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Formation of an adherent hematopoietic expansion culture using fucoidan

Citation

Irhimeh, MR and Fitton, JH and Ko, K and Lowenthal, RM and Nordon, RE, Formation of an adherent hematopoietic expansion culture using fucoidan, Annals of Hematology, 90, (9) pp. 1005-1015. ISSN 0939-5555 (2011) [Refereed Article]


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Copyright Statement

Copyright 2011 Springer-Verlag

DOI: doi:10.1007/s00277-011-1185-4

Abstract

Expansion 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.

Item Details

Item Type:Refereed Article
Keywords:adherent culture, hematopoietic stem cells, CD34+, cytokines, factorial design experiments, seaweed, polysaccharides, fucoidan
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Haematology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Irhimeh, MR (Dr Mohammad Irhimeh)
Author:Lowenthal, RM (Professor Ray Lowenthal)
ID Code:77806
Year Published:2011
Web of Science® Times Cited:3
Deposited By:Medicine (Discipline)
Deposited On:2012-05-30
Last Modified:2012-10-15
Downloads:2 View Download Statistics

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