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

C. E. Severn, A. M. Eissa, C. R. Langford, A. Parker, M. Walker, J. G.G. Dobbe, G. J. Streekstra, N. R. Cameron, A. M. Toye*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

7 Citations (Scopus)
246 Downloads (Pure)

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.

Original languageEnglish
Article number119533
Number of pages13
JournalBiomaterials
Volume225
Early online date4 Oct 2019
DOIs
Publication statusPublished - 1 Dec 2019

Structured keywords

  • Bristol BioDesign Institute

Keywords

  • Three-dimensional
  • Erythroid
  • Scaffold
  • polyHIPE
  • Haematopoietic
  • Jagged-1
  • Functionalisation
  • synthetic biology

Fingerprint Dive into the research topics of 'Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche'. Together they form a unique fingerprint.

Cite this