Engineered niches support the development of human dendritic cells in humanized mice

Giorgio Anselmi, Kristine Vaivode, Charles-Antoine Dutertre, Pierre Bourdely, Yoann Missolo-Koussou, Evan Newell, Oliver Hickman, Kristie Wood, Alka Saxena, Julie Helft, Florent Ginhoux and Pierre Guermonprez ()
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Giorgio Anselmi: King’s College London
Kristine Vaivode: King’s College London
Charles-Antoine Dutertre: A*STAR
Pierre Bourdely: King’s College London
Yoann Missolo-Koussou: INSERM U932 & SiRIC, Translational Immunotherapy Team
Evan Newell: A*STAR
Oliver Hickman: King’s College London
Kristie Wood: National Institute of Health Research Biomedical Research Centre at Guy’s and St Thomas’ Hospital and King’s College London
Alka Saxena: National Institute of Health Research Biomedical Research Centre at Guy’s and St Thomas’ Hospital and King’s College London
Julie Helft: INSERM U932 & SiRIC, Translational Immunotherapy Team
Florent Ginhoux: A*STAR
Pierre Guermonprez: King’s College London

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract Classical dendritic cells (cDCs) are rare sentinel cells specialized in the regulation of adaptive immunity. Modeling cDC development is crucial to study cDCs and harness their therapeutic potential. Here we address whether cDCs could differentiate in response to trophic cues delivered by mesenchymal components of the hematopoietic niche. We find that mesenchymal stromal cells engineered to express membrane-bound FLT3L and stem cell factor (SCF) together with CXCL12 induce the specification of human cDCs from CD34+ hematopoietic stem and progenitor cells (HSPCs). Engraftment of engineered mesenchymal stromal cells (eMSCs) together with CD34+ HSPCs creates an in vivo synthetic niche in the dermis of immunodeficient mice driving the differentiation of cDCs and CD123+AXL+CD327+ pre/AS-DCs. cDC2s generated in vivo display higher levels of resemblance with human blood cDCs unattained by in vitro-generated subsets. Altogether, eMSCs provide a unique platform recapitulating the full spectrum of cDC subsets enabling their functional characterization in vivo.

Date: 2020
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DOI: 10.1038/s41467-020-15937-y

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