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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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Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche. / Severn, C. E.; Eissa, A. M.; Langford, C. R.; Parker, A.; Walker, M.; Dobbe, J. G.G.; Streekstra, G. J.; Cameron, N. R.; Toye, A. M.

In: Biomaterials, Vol. 225, 119533, 01.12.2019.

Research output: Contribution to journalArticle (Academic Journal)

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Severn, C. E., Eissa, A. M., Langford, C. R., Parker, A., Walker, M., Dobbe, J. G. G., Streekstra, G. J., Cameron, N. R., & 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]. https://doi.org/10.1016/j.biomaterials.2019.119533

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Severn, C. E. ; Eissa, A. M. ; Langford, C. R. ; Parker, A. ; Walker, M. ; Dobbe, J. G.G. ; Streekstra, G. J. ; Cameron, N. R. ; Toye, A. M. / Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche. In: Biomaterials. 2019 ; Vol. 225.

Bibtex

@article{dd526a2e3e5b4647ac4d1d7784cd4ea6,
title = "Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche",
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.",
keywords = "Three-dimensional, Erythroid, Scaffold, polyHIPE, Haematopoietic, Jagged-1, Functionalisation, synthetic biology",
author = "Severn, {C. E.} and Eissa, {A. M.} and Langford, {C. R.} and A. Parker and M. Walker and Dobbe, {J. G.G.} and Streekstra, {G. J.} and Cameron, {N. R.} and Toye, {A. M.}",
year = "2019",
month = dec,
day = "1",
doi = "10.1016/j.biomaterials.2019.119533",
language = "English",
volume = "225",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche

AU - Severn, C. E.

AU - Eissa, A. M.

AU - Langford, C. R.

AU - Parker, A.

AU - Walker, M.

AU - Dobbe, J. G.G.

AU - Streekstra, G. J.

AU - Cameron, N. R.

AU - Toye, A. M.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

KW - Three-dimensional

KW - Erythroid

KW - Scaffold

KW - polyHIPE

KW - Haematopoietic

KW - Jagged-1

KW - Functionalisation

KW - synthetic biology

UR - http://www.scopus.com/inward/record.url?scp=85072961574&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2019.119533

DO - 10.1016/j.biomaterials.2019.119533

M3 - Article (Academic Journal)

C2 - 31610389

AN - SCOPUS:85072961574

VL - 225

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

M1 - 119533

ER -