Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells

Hannah Donnelly, Ewan Ross, Yinbo Xiao, Rio Hermantara, Aqeel F. Taqi, W. Sebastian Doherty-Boyd, Jennifer Cassels, Penelope. M. Tsimbouri, Karen M. Dunn, Jodie Hay, Annie Cheng, R. M. Dominic Meek, Nikhil Jain, Christopher West, Helen Wheadon, Alison M. Michie, Bruno Peault, Adam G. West, Manuel Salmeron-Sanchez () and Matthew J. Dalby ()
Additional contact information
Hannah Donnelly: University of Glasgow
Ewan Ross: University of Glasgow
Yinbo Xiao: University of Glasgow
Rio Hermantara: University of Glasgow
Aqeel F. Taqi: University of Glasgow
W. Sebastian Doherty-Boyd: University of Glasgow
Jennifer Cassels: University of Glasgow
Penelope. M. Tsimbouri: University of Glasgow
Karen M. Dunn: University of Glasgow
Jodie Hay: University of Glasgow
Annie Cheng: University of Glasgow
R. M. Dominic Meek: Queen Elizabeth University Hospital
Nikhil Jain: Queen Elizabeth Hospital
Christopher West: The University of Edinburgh
Helen Wheadon: University of Glasgow
Alison M. Michie: University of Glasgow
Bruno Peault: The University of Edinburgh
Adam G. West: University of Glasgow
Manuel Salmeron-Sanchez: University of Glasgow
Matthew J. Dalby: University of Glasgow

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50054-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50054-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50054-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().