Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells.

Szczegóły
Abstrakt

Tytuł:: Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells.
Autorzy:: Laustsen A; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
van der Sluis RM; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark.
Gris-Oliver A; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Hernández SS; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Cemalovic E; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.; Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway.
Tang HQ; Department of Obstetrics and Gynaecology, Aarhus University Hospital, Aarhus, Denmark.
Pedersen LH; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Department of Obstetrics and Gynaecology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Uldbjerg N; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Jakobsen MR; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Bak RO; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark.
Źródło:: ELife [Elife] 2021 Sep 02; Vol. 10. Date of Electronic Publication: 2021 Sep 02.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
MeSH Terms:: Dendritic Cells*/cytology
Dendritic Cells*/drug effects
Hematopoietic Stem Cells*/cytology
Hematopoietic Stem Cells*/drug effects
Ascorbic Acid/*pharmacology
Cell Culture Techniques/*methods
Cell Differentiation/*drug effects
Cells, Cultured ; Culture Media/chemistry ; Humans ; Immunotherapy
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Contributed Indexing:: Keywords: TLR7; TLR9; ascorbic acid; cHSPC; dendritic cells; differentiation; ex; hematopoietic stem cells; human; immunology; immunotherapy; inflammation; pDC; plasmacytoid; vitamin c; vivo
Molecular Sequence:: Dryad 10.5061/dryad.69p8cz92z
Substance Nomenclature:: 0 (Culture Media)
PQ6CK8PD0R (Ascorbic Acid)
Entry Date(s):: Date Created: 20210902 Date Completed: 20211101 Latest Revision: 20211101
Update Code:: 20240105
PubMed Central ID:: PMC8445615
DOI:: 10.7554/eLife.65528
PMID:: 34473049
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Plasmacytoid dendritic cells (pDCs) constitute a rare type of immune cell with multifaceted functions, but their potential use as a cell-based immunotherapy is challenged by the scarce cell numbers that can be extracted from blood. Here, we systematically investigate culture parameters for generating pDCs from hematopoietic stem and progenitor cells (HSPCs). Using optimized conditions combined with implementation of HSPC pre-expansion, we generate an average of 465 million HSPC-derived pDCs (HSPC-pDCs) starting from 100,000 cord blood-derived HSPCs. Furthermore, we demonstrate that such protocol allows HSPC-pDC generation from whole-blood HSPCs, and these cells display a pDC phenotype and function. Using GMP-compliant medium, we observe a remarkable loss of TLR7/9 responses, which is rescued by ascorbic acid supplementation. Ascorbic acid induces transcriptional signatures associated with pDC-specific innate immune pathways, suggesting an undescribed role of ascorbic acid for pDC functionality. This constitutes the first protocol for generating pDCs from whole blood and lays the foundation for investigating HSPC-pDCs for cell-based immunotherapy.
Competing Interests: AL, SH, EC, HT, LP, NU Aarhus University has filed a patent related to this work with AL, MRJ and ROB as co-inventors. AL holds equity in the Danish company UNIKUM Therapeutics ApS. AL is a full-time employee at UNIKUM Therapeutics ApS. Rv None, AG none, MJ Aarhus University has filed a patent related to this work with AL, MRJ and ROB as co-inventors. MRJ holds equity in the Danish company UNIKUM Therapeutics ApS. MRJ serves on the board of directors of UNIKUM Therapeutics ApS, RB Aarhus University has filed a patent related to this work with AL, MRJ and ROB as co-inventors. ROB holds equity in the Danish company UNIKUM Therapeutics ApS. ROB is a part-time employee at UNIKUM Therapeutics ApS. ROB holds equity in Graphite Bio.
(© 2021, Laustsen et al.)

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