Comparison of Natural Killer Cells Differentiated from Various Pluripotent Stem Cells

Author:

Han Jongsuk1ORCID,Son Hyeongbin1ORCID,Jung Daun2,Kim Ki-Yeon2,Jin Chaeyeon1ORCID,Hwang Hyeonwook1,Kang Soon-Suk3,Mitalipov Shoukhrat4,An Hee-Jung2,Lee Yeonmi13,Kang Eunju135ORCID

Affiliation:

1. Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea

2. Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam-si 13496, Gyeonggi-do, Republic of Korea

3. Cell Therapy 3 Center, CHA Advanced Research Institute, CHA Bundang Medical Center, Sungnam-si 13488, Gyeonggi-do, Republic of Korea

4. Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland, OR 97239, USA

5. Department of Biochemistry, School of Medicine, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea

Abstract

Allogeneic natural killer (NK) cell therapy has been effective in treating cancer. Many studies have tested NK cell therapy using human pluripotent stem cells (hPSCs). However, the impacts of the origin of PSC-NK cells on competence are unclear. In this study, several types of hPSCs, including human-induced PSCs (hiPSCs) generated from CD34+, CD3−CD56+, and CD56− cells in umbilical cord blood (UCB), three lines of human embryonic stem cells (hESCs, ES-1. ES-2 and ES-3) and MHC I knockout (B2M-KO)-ESCs were used to differentiate into NK cells and their capacities were analyzed. All PSC types could differentiate into NK cells. Among the iPSC-derived NK cells (iPSC-NKs) and ESC-derived NK cells (ES-NKs), 34+ iPSCs and ES-3 had a higher growth rate and cytotoxicity, respectively, ES-3 also showed better efficacy than 34+ iPSCs. B2M-KO was similar to the wild type. These results suggest that the screening for differentiation of PSCs into NK cells prior to selecting the PSC lines for the development of NK cell immunotherapy is an essential process for universal allotransplantation, including the chimeric antigen receptor (CAR).

Funder

Korea Health Industry Development Institute

Korean government

Publisher

MDPI AG

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