HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells
Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches b...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/8873383 |
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| author | Yoo-Wook Kwon Hyo-Suk Ahn Jin-Woo Lee Han-Mo Yang Hyun-Jai Cho Seok Joong Kim Shin-Hyae Lee Heung-Mo Yang Hyun-Duk Jang Sung Joo Kim Hyo-Soo Kim |
| author_facet | Yoo-Wook Kwon Hyo-Suk Ahn Jin-Woo Lee Han-Mo Yang Hyun-Jai Cho Seok Joong Kim Shin-Hyae Lee Heung-Mo Yang Hyun-Duk Jang Sung Joo Kim Hyo-Soo Kim |
| author_sort | Yoo-Wook Kwon |
| collection | DOAJ |
| description | Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-γ. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4+ T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors. |
| format | Article |
| id | doaj-art-f0c14d6b062e4c4284a45bad9dbc846d |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-f0c14d6b062e4c4284a45bad9dbc846d2025-02-03T05:52:57ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/88733838873383HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic CellsYoo-Wook Kwon0Hyo-Suk Ahn1Jin-Woo Lee2Han-Mo Yang3Hyun-Jai Cho4Seok Joong Kim5Shin-Hyae Lee6Heung-Mo Yang7Hyun-Duk Jang8Sung Joo Kim9Hyo-Soo Kim10Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of KoreaStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of KoreaStrategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of KoreaCardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of KoreaCardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of KoreaToolGen, Inc., #1204, Byucksan Digital Valley 6-cha, 219 Gasan Digital 1-ro, Geumcheon-gu, Seoul 08501, Republic of KoreaSK Chemical, Life Science Business, Clinical Research Team, Gyeonggi-do, 13494, Republic of KoreaGenNBio, Inc., 422, Teheran-ro, Gangnam-gu, Seoul 06193, Republic of KoreaStrategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of KoreaGenNBio, Inc., 422, Teheran-ro, Gangnam-gu, Seoul 06193, Republic of KoreaStrategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of KoreaAlthough human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-γ. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4+ T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors.http://dx.doi.org/10.1155/2021/8873383 |
| spellingShingle | Yoo-Wook Kwon Hyo-Suk Ahn Jin-Woo Lee Han-Mo Yang Hyun-Jai Cho Seok Joong Kim Shin-Hyae Lee Heung-Mo Yang Hyun-Duk Jang Sung Joo Kim Hyo-Soo Kim HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells Stem Cells International |
| title | HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells |
| title_full | HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells |
| title_fullStr | HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells |
| title_full_unstemmed | HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells |
| title_short | HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells |
| title_sort | hla dr genome editing with talens in human ipscs produced immune tolerant dendritic cells |
| url | http://dx.doi.org/10.1155/2021/8873383 |
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