دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells.
المؤلفون: Donnelly H; Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom., Ross E; Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom., Xiao Y; Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom., Hermantara R; School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, G61 1QH, United Kingdom., Taqi AF; School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, G61 1QH, United Kingdom., Doherty-Boyd WS; Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom., Cassels J; School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom., Tsimbouri PM; Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom., Dunn KM; School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom., Hay J; School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom., Cheng A; Centre for the Cellular Microenvironment, Division of Biomedical Engineering, James Watt School of Engineering, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom., Meek RMD; Department of Trauma and Orthopaedics, Queen Elizabeth University Hospital, Glasgow, G51 4TF, United Kingdom., Jain N; Institute of Inflammation and Ageing, University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom., West C; MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom., Wheadon H; School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom., Michie AM; School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom., Peault B; MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom., West AG; School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, G61 1QH, United Kingdom., Salmeron-Sanchez M; Centre for the Cellular Microenvironment, Division of Biomedical Engineering, James Watt School of Engineering, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom. manuel.salmeron-sanchez@glasgow.ac.uk., Dalby MJ; Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom. matthew.dalby@glasgow.ac.uk.
المصدر: Nature communications [Nat Commun] 2024 Jul 10; Vol. 15 (1), pp. 5791. Date of Electronic Publication: 2024 Jul 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Hematopoietic Stem Cells*/metabolism , Hematopoietic Stem Cells*/cytology , Nestin*/metabolism , Nestin*/genetics , Extracellular Matrix*/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit*/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit*/genetics, Animals ; Mice ; Stem Cell Niche ; Hydrogels/chemistry ; Bioengineering/methods ; Humans ; Mesenchymal Stem Cells/metabolism ; Mesenchymal Stem Cells/cytology ; Hematopoietic Stem Cell Transplantation ; Antigens, CD34/metabolism ; Collagen Type I/metabolism ; Cell Differentiation ; Mice, Inbred C57BL
مستخلص: 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.
(© 2024. The Author(s).)
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معلومات مُعتمدة: BB/N018419/1 RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); EP/P001114/1 RCUK | Engineering and Physical Sciences Research Council (EPSRC); MR/R005567/1 RCUK | Medical Research Council (MRC)
المشرفين على المادة: 0 (Nestin)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Hydrogels)
0 (Antigens, CD34)
0 (Collagen Type I)
تواريخ الأحداث: Date Created: 20240710 Date Completed: 20240710 Latest Revision: 20240714
رمز التحديث: 20240714
مُعرف محوري في PubMed: PMC11237034
DOI: 10.1038/s41467-024-50054-0
PMID: 38987295
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-50054-0