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Generation of hypoimmunogenic human pluripotent stem cells
Open accessAbstract
Significance: To enable cell therapy on a broader scale, the development of universal donor stem cell products that can be administered to multiple patients in need has been proposed, yet a strategy controlling both adaptive and innate immune rejection has not been reported. In this study, we employed multiplex genome editing to selectively ablate the highly polymorphic HLA class Ia and class II molecules and introduced the immunoregulatory factors PD-L1, HLA-G, and CD47 to control T cell- and NK cell-mediated immune responses and macrophage engulfment in vitro and in vivo. Our strategy demonstrates the power of cell engineering and informs future studies aiming to generate “off-the-shelf” universal cell products that may make cell therapy available to a larger pool of patients.
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“These cells could be differentiated into endothelial cells or vascular smooth muscle cells and demonstrated improved survival in co-cultures with T-cells, NK cells, and macrophages.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [119]
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Cites
PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Gordon, S. R., Maute, R. L., Dulken, B. W., Hutter, G., George, B. M., McCracken, M. N., Gupta, R., Tsai, J. M., Sinha, R., Corey, D., et al. (2017) · Nature · doi:10.1038/nature22396 · Cited by 2,247
Six-of-the-best: unique contributions of γδ T cells to immunology
Vantourout, P., & Hayday, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3384 · Cited by 1,232
Development and function of human innate immune cells in a humanized mouse model
Rongvaux, A., Willinger, T., Martinek, J., Strowig, T., Gearty, S. V., Teichmann, L. L., Saito, Y., Marches, F., Halene, S., Palucka, A. K., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2858 · Cited by 789
PD-1 signaling in primary T cells
Riley, J. L. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00767.x · Cited by 778 · cited 1×
“To counteract any residual T cell activity, we decided to knock in PD-L1, directly suppressing T cell responses (27).”
BackgroundEfficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9
Mandal, P. K., Ferreira, L. M. R., Collins, R., Meissner, T. B., Boutwell, C. L., Friesen, M., Vrbanac, V., Garrison, B. S., Stortchevoi, A., Bryder, D., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.10.004 · Cited by 475
Molecular Obstacles to Clinical Translation of iPSCs
Tapia, N., & Schöler, H. R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.06.017 · Cited by 141
Research works printed but not linked: 38
- 10.1155/2014/518135 · DOI
- 10.1016/B978-0-12-801185-0.00013-1 · DOI
- 10.1038/mt.2013.59 · DOI · Paper page
- 10.5966/sctm.2015-0049 · DOI
- 10.1161/JAHA.118.010239 · DOI
- 10.1186/s40659-015-0051-6 · DOI
- 10.1016/j.it.2017.01.009 · DOI
- 10.1073/pnas.95.9.5199 · DOI
- 10.1016/j.stem.2013.11.014 · DOI
- 10.1016/j.healun.2007.03.007 · DOI
- 10.1093/ndt/16.suppl_6.150 · DOI
- 10.1172/JCI200420483 · DOI
- 10.1146/annurev.immunol.19.1.225 · DOI
- 10.4049/jimmunol.178.12.7503 · DOI
- 10.1038/nbt.3860 · DOI · Paper page
- 10.1038/35869 · DOI
- 10.1038/icb.2010.78 · DOI
- 10.1126/science.274.5288.792 · DOI
- 10.1126/scitranslmed.aae0501 · DOI
- 10.1016/j.cell.2009.05.046 · DOI
- 10.1016/j.stem.2013.03.006 · DOI · Paper page
- 10.1016/S0960-9822(98)70014-4 · DOI
- 10.1016/S0960-9822(02)00481-5 · DOI
- 10.18632/oncotarget.12150 · DOI
- 10.3389/fimmu.2016.00351 · DOI
- 10.1038/nrc3179 · DOI · Paper page
- Lee N, Goodlett DR, Ishitani A, Marquardt H, Geraghty DE (1998) HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. J Immunol 160:4951–4960. · DOI
- 10.1073/pnas.142298299 · DOI
- 10.1161/CIRCRESAHA.111.249243 · DOI
- 10.1007/s00281-003-0139-x · DOI
- 10.1111/ajt.12589 · DOI
- 10.1097/MOT.0000000000000262 · DOI
- 10.1038/nm1431 · DOI
- 10.1016/j.jim.2014.02.011 · DOI
- 10.1038/s41592-018-0071-6 · DOI
- 10.1056/NEJMsr040330 · DOI
- 10.1038/ncb3205 · DOI
- 10.1084/jem.20071143 · DOI
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Baryawno, N., Przybylski, D., Kowalczyk, M. S., Kfoury, Y. S., Sévère, N., Gustafsson, K. U., Kokkaliaris, K. D., Mercier, F., Tabaka, M., Hofree, M., et al. (2019) · Cell · doi:10.1016/j.cell.2019.04.040 · Cited by 916
Next-generation regulatory T cell therapy
Ferreira, L. M. R., Müller, Y. D., Bluestone, J. A., & Tang, Q. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0041-4 · Cited by 491
Self-citationEngineering the next generation of cell-based therapeutics
Bashor, C. J., Hilton, I. B., Bandukwala, H. S., Smith, D. M., & Omid Veiseh, A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00476-6 · Cited by 472
Chang, Y., Cai, X., Syahirah, R., Yao, Y., Xu, Y., Jin, G., Bhute, V. J., Torregrosa‐Allen, S. E., Elzey, B. D., Won, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37872-4 · Cited by 245
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Zipser, C., Cragg, J., Guest, J., Fehlings, M., Jutzeler, C., Anderson, A., & Curt, A. (2022) · Lancet Neurology · doi:10.1016/s1474-4422(21)00464-6 · Cited by 212
Metadata
- Authors
- Han, X., Wang, M., Duan, S., Franco, P. J., Kenty, J. H.-R., Hedrick, P., Xia, Y., Allen, A., Ferreira, L. M. R., Strominger, J. L., Melton, D. A., Meissner, T. B., & Cowan, C. A.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Broad Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-04-30
- Volume
- 116
- Issue
- 21
- Pages
- 10441-10446
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6535035
- OpenAlex
- W2943378944
- Cited by
- 363
- References
- 0
- Citations by year
- 2026: 45 · 2025: 52 · 2024: 49 · 2023: 62 · 2022: 58 · 2021: 53 · 2020: 34 · 2019: 10
- FWCI
- 12.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Harvard University | Harvard Stem Cell Institute (DP-0155-16-00)
- Blavatnik Biomedical Accelerator (no number)
- JDRF (3-SRA-2017-363-S-B)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- human pluripotent stem cells, multiplex genome editing, PD-L1, HLA-G, CD47, macrophage engulfment, cell therapy
- MeSH terms
- Cell Line, Genes, MHC Class II, Genes, MHC Class I, Genetic Engineering, Humans, Pluripotent Stem Cells, Gene Knockout Techniques, CRISPR-Cas Systems
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