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Review

Differentiating Induced Pluripotent Stem Cells into Natural Killer Cells for Adoptive Cell Immunotherapies—Comparative Characterization of Current Protocols

1
Research Centre for Medical Genetics, Moskvorechye Str. 1, Moscow 115522, Russia
2
Research Institute of Molecular and Cellular Medicine, Peoples’ Friendship University of Russia, Miklukho-Maklaya Str. 6, Moscow 117198, Russia
3
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Samory Mashela Str. 1, Moscow 117198, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(3), 1107; https://doi.org/10.3390/ijms26031107
Submission received: 2 December 2024 / Revised: 23 January 2025 / Accepted: 23 January 2025 / Published: 27 January 2025
(This article belongs to the Special Issue Stem Cells in Human Health and Diseases)

Abstract

Cancers constitute a leading cause of mortality. Chimeric antigen receptor (CAR) cell therapies provide breakthrough solutions for various cancers while posing considerable risks of immunological side reactions. Of various cytotoxic lymphocyte subsets, natural killer (NK) cells are considered the least immunogenic. Obtaining viable NK cells with stable phenotypes in quantities sufficient for modification is technologically challenging. The candidate sources include primary mononuclear cell cultures and immortalized NK cell lines; alternatively, the clinical-grade NK cells can be differentiated from induced pluripotent stem cells (iPSCs) by a good manufacturing practice (GMP)-compatible xeno-free protocol. In this review, we analyze existing protocols for targeted differentiation of human iPSCs into NK cells with a focus on xeno-free requirements.
Keywords: adoptive NK cell therapy; induced pluripotent stem cells; xeno-free platforms adoptive NK cell therapy; induced pluripotent stem cells; xeno-free platforms

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MDPI and ACS Style

Budagova, T.; Efremova, A.; Usman, N.; Mokrousova, D.; Goldshtein, D. Differentiating Induced Pluripotent Stem Cells into Natural Killer Cells for Adoptive Cell Immunotherapies—Comparative Characterization of Current Protocols. Int. J. Mol. Sci. 2025, 26, 1107. https://doi.org/10.3390/ijms26031107

AMA Style

Budagova T, Efremova A, Usman N, Mokrousova D, Goldshtein D. Differentiating Induced Pluripotent Stem Cells into Natural Killer Cells for Adoptive Cell Immunotherapies—Comparative Characterization of Current Protocols. International Journal of Molecular Sciences. 2025; 26(3):1107. https://doi.org/10.3390/ijms26031107

Chicago/Turabian Style

Budagova, Tatiana, Anna Efremova, Natalia Usman, Diana Mokrousova, and Dmitry Goldshtein. 2025. "Differentiating Induced Pluripotent Stem Cells into Natural Killer Cells for Adoptive Cell Immunotherapies—Comparative Characterization of Current Protocols" International Journal of Molecular Sciences 26, no. 3: 1107. https://doi.org/10.3390/ijms26031107

APA Style

Budagova, T., Efremova, A., Usman, N., Mokrousova, D., & Goldshtein, D. (2025). Differentiating Induced Pluripotent Stem Cells into Natural Killer Cells for Adoptive Cell Immunotherapies—Comparative Characterization of Current Protocols. International Journal of Molecular Sciences, 26(3), 1107. https://doi.org/10.3390/ijms26031107

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