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EBSCO

https://doi.org/10.14300/mnnc.2024.19037

Activation of human pluripotent stem cell-derived dendritic cells by cancer cell co-culture

[Experimental medicine]
Igor Mikhailovich Samokhvalov; Konstantin Dmitrievich Malyi; Elizaveta Sergeevna Ageeva; Evelina Talytovna Degirmendzhi; Anna Konstantinovna Gurtovaya; Remzie Narimanovna Ablaeva; Peter Sergeevich Trofimov; Anatoly Vladimirovich Kubyshkin;

Human pluripotent stem cells (hPSCs) are considered a source of cell therapy. Dendritic cells (DCs) derived from hPSCs (hPSC DCs) are viewed as similar to fetal DCs. The latter, while mediating immune suppression, maintain fetal homeostasis. This study looks at the outcomes of a protocol designed for massive and long-term generation of hPSC-DCs in a serum-free cell culture. When cultured in serum-free media, the newly generated pure populations of immature hPSC-DCs featured significant stability. Such DCs exhibited the typical morphology, active phagocytosis, and were highly motile. The cells expressed on the outer cell membrane specific well-known DC markers, CD11c, CD86, and CD45, while were negative for CD14, the key macrophage marker. Attempts to activate the hPSC-DCs through proinflammatory factors failed to induce IL-12 secretion and cell surface expression of HLA-DR. Yet, they elicited the expression of several genes encoding markers that belong to the conventional DC subset 1 (cDC1). Co-culturing hPSC-DCs with thyroid cancer cells entailed secretion of IL-12 and, in a fraction of the population, strong cell surface expression of HLA-DR and other markers of activated DCs. Our observations suggest that hPSC-DCs require necrotic cancer cell-derived damage-associated molecular patterns (DAMPs) for their activation.

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Keywords: dendritic cells, pluripotent stem cells, hematopoiesis, differentiation, cancer cells