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

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 generatin...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	ascorbic acid plasmacytoid pDC dendritic cells hematopoietic stem cells vitamin c Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6f3798286f634c3eb305fef770b61810
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spelling	oai:doaj.org-article:6f3798286f634c3eb305fef770b618102021-11-15T07:04:11ZAscorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells10.7554/eLife.655282050-084Xe65528https://doaj.org/article/6f3798286f634c3eb305fef770b618102021-09-01T00:00:00Zhttps://elifesciences.org/articles/65528https://doaj.org/toc/2050-084XPlasmacytoid 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.Anders LaustsenRenée M van der SluisAlbert Gris-OliverSabina Sánchez HernándezEna CemalovicHai Q TangLars Henning PedersenNiels UldbjergMartin R JakobsenRasmus O BakeLife Sciences Publications Ltdarticleascorbic acidplasmacytoidpDCdendritic cellshematopoietic stem cellsvitamin cMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ascorbic acid plasmacytoid pDC dendritic cells hematopoietic stem cells vitamin c Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	ascorbic acid plasmacytoid pDC dendritic cells hematopoietic stem cells vitamin c Medicine R Science Q Biology (General) QH301-705.5 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 Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells
description	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.
format	article
author	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
author_facet	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
author_sort	Anders Laustsen
title	Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells
title_short	Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells
title_full	Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells
title_fullStr	Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells
title_full_unstemmed	Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells
title_sort	ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/6f3798286f634c3eb305fef770b61810
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Ascorbic acid supports ex vivo generation of plasmacytoid dendritic cells from circulating hematopoietic stem cells

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