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On November 8, 2022, the research team of Wang Jinyong, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, and Beijing Institute of Stem Cell and Regenerative Medicine, published an online report on Cell Discovery Research paper on the Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells
.
In this study, high-purity side plate mesoblast cells and trophoblasts derived from human pluripotent stem cells were used for the first time to assemble organoid aggregates, and the gas-liquid interface was used for culture induction to achieve in vitro regeneration
of NK cells (iNK).
Compared with traditional methods, this induction strategy has the characteristics of
short time-consuming, high yield, high maturity, no need for secondary amplification, and low cost.
Killing tests for multiple tumor types confirmed broad-spectrum, highly effective anti-tumor activity
of iNK cells.
This study provides a new method
for the large-scale preparation of human pluripotent stem cell-derived regenerative iNK cells.
NK cells can directly kill various tumor cells in a broad spectrum, have few toxic side effects, and adoptive treatment does not require matching, which is an ideal spot immune cell therapy drug
.
At present, NK cells for clinical treatment are mainly derived from human tissues such as umbilical cord blood and peripheral blood, and these naturally derived NK cells are heterogeneous, with high preparation cost, low yield, and preparation cycle limited by human tissue
accessibility.
Human pluripotent stem cell-induced differentiation-derived NK cells are expected to solve the above problems
.
The traditional method of differentiation and regeneration of NK cells from pluripotent stem cells requires going through the embryoid body intermediate stage, and further large-scale expansion of feeding cells with the help of expansion feeder cells, and the activity of iNK cells obtained is poor
.
Wang Jinyong's research group has developed an organoid aggregate assembly method that does not rely on embryoid bodies and is based on the side plate mesoderm as the starting seed cell, so as to realize the efficient regeneration
of iNK cells.
In the 27-day induction cycle, millions of pluripotent stem cells can be invested to export more than one billion iNK cells
.
In this study, regenerative iNK cells are highly expressed with classical cytotoxic granules (perforin and granzyme B), apoptosis-inducing-related ligands (FasL and TRAIL), and a range of NK cell activating and inhibitory receptors
.
Functionally, iNK cells can kill human tumor cells
by directly poisoning, inducing target apoptosis, and antibody-dependent cell-mediated cytotoxicity.
This study provides key technical support for the large-scale production of off-the-shelf, universal and regenerative NK cell drugs, promotes the clinical transformation and application of iNK cells, and benefits patients
.
iNK cells prepared based on this technology have been used in clinical trials
.
Huang Dehao, postdoctoral fellow of the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Li Jianhuan, doctoral student of Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, and Dr.
Hu Fangxiao and Dr.
Xia Chengxiang, young scholars of Beijing Institute of Stem Cell and Regenerative Medicine, are the co-first authors of the paper, and Professor Wang Jinyong is the corresponding author
of the paper.
The research was supported
by the National Key Research and Development Program, the Strategic Leading Science and Technology Project of the Chinese Academy of Sciences, and the National Natural Science Foundation of China Outstanding Youth Fund.
The research has also been strongly supported
by advanced platform departments such as the Laboratory Animal Center, the Instrument Center, and the National Stem Cell Resource Bank of the Institute of Zoology, Chinese Academy of Sciences.
Original link: https://doi.
org/10.
1038/s41421-022-00467-2
Figure: Schematic diagram of human pluripotent stem cell-induced regenerative NK cell technology