Feeder-free differentiation of human iPSCs into natural killer cells with cytotoxic potential against malignant brain rhabdoid tumor cells  

作　　者：Sonia Kiran Yu Xue Drishty B.Sarker Yan Li Qing-Xiang Amy Sang 

机构地区：[1]Department of Chemistry and Biochemistry,Florida State University,Tallahassee,FL 32306-4390,USA [2]Department of Chemical and Biomedical Engineering,FAMU-FSU College of Engineering,Florida State University,Tallahassee,FL,32310-6046,USA [3]Institute of Molecular Biophysics,Florida State University,Tallahassee,FL,32306-4380,USA

出　　处：《Bioactive Materials》2024年第6期301-316,共16页生物活性材料（英文）

基　　金：supported by the National Science Foundation(CBET-1652992 and CBET-1917618 to Y.L.).

摘　　要：Natural killer(NK)cells are cytotoxic immune cells that can eliminate target cells without prior stimulation.Human induced pluripotent stem cells(iPSCs)provide a robust source of NK cells for safe and effective cell-based immunotherapy against aggressive cancers.In this in vitro study,a feeder-free iPSC differentiation was performed to obtain iPSC-NK cells,and distinct maturational stages of iPSC-NK were characterized.Mature cells of CD56^(bright)CD16^(bright)phenotype showed upregulation of CD56,CD16,and NK cell activation markers NKG2D and NKp46 upon IL-15 exposure,while exposure to aggressive atypical teratoid/rhabdoid tumor(ATRT)cell lines enhanced NKG2D and NKp46 expression.Malignant cell exposure also increased CD107a degranulation markers and stimulated IFN-γsecretion in activated NK cells.CD56^(bright)CD16^(bright)iPSC-NK cells showed a ratio-dependent killing of ATRT cells,and the percentage lysis of CHLA-05-ATRT was higher than that of CHLA-02-ATRT.The iPSC-NK cells were also cytotoxic against other brain,kidney,and lung cancer cell lines.Further NK maturation yielded CD56^(-ve) CD16^(bright)cells,which lacked activation markers even after exposure to interleukins or ATRT cells-indicating diminished cytotoxicity.Generation and characterization of different NK phenotypes from iPSCs,coupled with their promising anti-tumor activity against ATRT in vitro,offer valuable insights into potential immunotherapeutic strategies for brain tumors.

关 键 词：Human induced pluripotent stem cells Natural killer cells Atypical teratoid rhabdoid tumor Cytotoxicity Cytokine activation 

分 类 号：R73[医药卫生—肿瘤]