Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells

Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells

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Abstract Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a source of off-the-shelf cell products for universal immune therapy.Conventional methods for iNK cell regeneration from hPSCs include embryoid body (EB) formation and feeder-based expansion steps, 30" Single True Convection Wall Oven which are time-consuming and cause instability and high costs of manufacturing.Here, we develop an EB-free, organoid aggregate method for NK cell regeneration from hPSCs.In a short time-window of 27-day induction, millions of hPSC input can output over billions of iNK cells without the necessity of NK cell expansion feeders.The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors.

Functionally, the iNK Womens Socks cells eradicate human tumor cells via mechanisms of direct cytotoxicity, apoptosis, and antibody-dependent cellular cytotoxicity.This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.