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Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche
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Severn, C. E., Eissa, Ahmed M., Langford, C. R., Parker, A., Walker, Marc, Dobbe, J. G. G., Streekstra, G .J., Cameron, Neil R. and Toye, A. M. (2019) Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche. Biomaterials, 225 . 119533. doi:10.1016/j.biomaterials.2019.119533 ISSN 0142-9612.
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Official URL: http://dx.doi.org/10.1016/j.biomaterials.2019.1195...
Abstract
Haematopoiesis, the process of blood production, occurs from a tiny contingent of haematopoietic stem cells (HSC) in highly specialised three-dimensional niches located within the bone marrow. When haematopoiesis is replicated using in vitro two-dimensional culture, HSCs rapidly differentiate, limiting self-renewal. Emulsion-templated highly porous polyHIPE foam scaffolds were chosen to mimic the honeycomb architecture of human bone. The unmodified polyHIPE material supports haematopoietic stem and progenitor cell (HSPC) culture, with successful culture of erythroid progenitors and neutrophils within the scaffolds. Using erythroid culture methodology, the CD34+ population was maintained for 28 days with continual release of erythroid progenitors. These cells are shown to spontaneously repopulate the scaffolds, and the accumulated egress can be expanded and grown at large scale to reticulocytes. We next show that the polyHIPE scaffolds can be successfully functionalised using activated BM(PEG)2 (1,8-bismaleimido-diethyleneglycol) and then a Jagged-1 peptide attached in an attempt to facilitate notch signalling. Although Jagged-1 peptide had no detectable effect, the BM(PEG)2 alone significantly increased cell egress when compared to controls, without depleting the scaffold population. This work highlights polyHIPE as a novel functionalisable material for mimicking the bone marrow, and also that PEG can influence HSPC behaviour within scaffolds.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > QC Physics Q Science > QP Physiology Q Science > QR Microbiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Physics | |||||||||
Library of Congress Subject Headings (LCSH): | Stem cells, Erythrocyte membranes, Tissue scaffolds, Hematopoietic stem cells | |||||||||
Journal or Publication Title: | Biomaterials | |||||||||
Publisher: | Elsevier Science BV | |||||||||
ISSN: | 0142-9612 | |||||||||
Official Date: | December 2019 | |||||||||
Dates: |
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Volume: | 225 | |||||||||
Article Number: | 119533 | |||||||||
DOI: | 10.1016/j.biomaterials.2019.119533 | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 11 November 2019 | |||||||||
Date of first compliant Open Access: | 11 November 2019 | |||||||||
RIOXX Funder/Project Grant: |
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