<p>Therapeutic correction of hemophilia A using 2D endothelial cells and multicellular 3D organoids derived from CRISPR/Cas9-engineered patient iPSCs</p>
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Chul-Yong | - |
dc.contributor.author | Lee, Gyunggyu | - |
dc.contributor.author | Kim, Gyeongmin | - |
dc.contributor.author | Woo, Dong-Hun | - |
dc.contributor.author | Han, Choongseong | - |
dc.contributor.author | Park, Han-Jin | - |
dc.contributor.author | Kim, Dong-Wook | - |
dc.contributor.author | Kim, Jong-Hoon | - |
dc.contributor.author | Son, Jeong Sang | - |
dc.contributor.author | Park, Ji Young | - |
dc.contributor.author | Kim, Hyo Jin | - |
dc.contributor.author | Chi, Kyun Yoo | - |
dc.contributor.author | Kim, Sang Kyum | - |
dc.date.accessioned | 2022-06-10T13:40:44Z | - |
dc.date.available | 2022-06-10T13:40:44Z | - |
dc.date.created | 2022-06-09 | - |
dc.date.issued | 2022-04 | - |
dc.identifier.issn | 0142-9612 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/141857 | - |
dc.description.abstract | The bleeding disorder hemophilia A (HA) is caused by a single-gene (F8) defect and its clinical symptom can be substantially improved by a small increase in the plasma coagulation factor VIII (FVIII) level. In this study, we used F8-defective human induced pluripotent stem cells from an HA patient (F8d-HA hiPSCs) and F8-corrected (F8c) HA hiPSCs produced by CRISPR/Cas9 genome engineering of F8d-HA hiPSCs. We obtained a highly enriched population of CD157(+) cells from CRISPR/Cas9-edited F8c-HA hiPSCs. These cells exhibited multiple cellular and functional phenotypes of endothelial cells (ECs) with significant levels of FVIII activity, which was not observed in F8d-HA hiPSC-ECs. After transplantation, the engineered F8c-HA hiPSC-ECs dramatically changed bleeding episodes in HA animals and restored plasma FVIII activity. Notably, grafting a high dose of ECs substantially reduced the bleeding time during multiple consecutive bleeding challenges in HA mice, demonstrating a robust hemostatic effect (90% survival). Furthermore, the engrafted ECs survived more than 3 months in HA mice and reversed bleeding phenotypes against lethal wounding challenges. We also produced F8c-HA hiPSC-derived 3D liver organoids by assembling three different cell types in microwell devices and confirmed its therapeutic effect in HA animals. Our data demonstrate that the combination of genome-engineering and iPSC technologies represents a novel modality that allows autologous cell-mediated gene therapy for treating HA. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCI LTD | - |
dc.subject | PLURIPOTENT STEM-CELLS | - |
dc.subject | FACTOR-VIII | - |
dc.subject | GENE-THERAPY | - |
dc.subject | COAGULATION | - |
dc.subject | MICROCARRIERS | - |
dc.subject | FACTOR-8 | - |
dc.subject | MODEL | - |
dc.title | <p>Therapeutic correction of hemophilia A using 2D endothelial cells and multicellular 3D organoids derived from CRISPR/Cas9-engineered patient iPSCs</p> | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Jong-Hoon | - |
dc.identifier.doi | 10.1016/j.biomaterials.2022.121429 | - |
dc.identifier.scopusid | 2-s2.0-85124962637 | - |
dc.identifier.wosid | 000789629600002 | - |
dc.identifier.bibliographicCitation | BIOMATERIALS, v.283 | - |
dc.relation.isPartOf | BIOMATERIALS | - |
dc.citation.title | BIOMATERIALS | - |
dc.citation.volume | 283 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Engineering | - |
dc.relation.journalResearchArea | Materials Science | - |
dc.relation.journalWebOfScienceCategory | Engineering, Biomedical | - |
dc.relation.journalWebOfScienceCategory | Materials Science, Biomaterials | - |
dc.subject.keywordPlus | PLURIPOTENT STEM-CELLS | - |
dc.subject.keywordPlus | FACTOR-VIII | - |
dc.subject.keywordPlus | GENE-THERAPY | - |
dc.subject.keywordPlus | COAGULATION | - |
dc.subject.keywordPlus | MICROCARRIERS | - |
dc.subject.keywordPlus | FACTOR-8 | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordAuthor | Hemophilia A | - |
dc.subject.keywordAuthor | Endothelial cells | - |
dc.subject.keywordAuthor | Induced pluripotent stem cells | - |
dc.subject.keywordAuthor | Genome-editing | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.