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

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DOI

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 lay the foundation for investigating HSPC-pDCs for cell-based immunotherapy
Original languageEnglish
Article numbere65528
JournaleLife
Volume10
Number of pages21
ISSN2050-084X
DOIs
Publication statusPublished - Sep 2021

    Research areas

  • ACTIVATION, BONE-MARROW, CANCER, Human, I INTERFERON-PRODUCTION, PERIPHERAL-BLOOD, PROGENITOR CELLS, SPI-B, T-CELLS, TLR7, TLR9, TRANSCRIPTION FACTOR E2-2, UMBILICAL-CORD BLOOD, ascorbic acid, cHSPC, dendritic cells, differentiation, ex, hematopoietic stem cells, immunotherapy, pDC, plasmacytoid, vitamin c, vivo

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