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

Huang D, Li J, Hu F, Weng Q, Wang T, Peng H, Wu B, Xia C, Wu H, Xiong J, Lin J, Lin Y, Wang Y, Zhang Q, Liu X, Liu L, Zheng X, Qiu H, Geng Y, Du X, Wang L, Hao J, Wang J.
Preprint from
3 December 2021


Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a promising “off-the-shelf” cell product for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryonic body-formation and feeder-based expansion steps, which bring instability, time-consuming, and high costs for manufacture. In this study, we develop an embryonic body-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time window of 27-day induction, millions of hPSC input can produce 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 cells eradicate human tumor cells by mechanisms of direct cytotoxity, 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.