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

Anders Laustsen, Renée M van der Sluis, Albert Gris-Oliver, Sabina Sánchez Hernández, Ena Cemalovic, Hai Q Tang, Lars Henning Pedersen, Niels Uldbjerg, Martin R Jakobsen, Rasmus O Bak
2021 eLife  
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
more » ... C-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.
doi:10.7554/elife.65528 pmid:34473049 pmcid:PMC8445615 fatcat:wbcii4acfnc7douaeo6qe53kgm