Cited 14 times in
Therapeutic correction of hemophilia A using 2D endothelial cells and multicellular 3D organoids derived from CRISPR/Cas9-engineered patient iPSCs
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김동욱 | - |
dc.contributor.author | 박철용 | - |
dc.date.accessioned | 2022-05-09T17:14:18Z | - |
dc.date.available | 2022-05-09T17:14:18Z | - |
dc.date.issued | 2022-04 | - |
dc.identifier.issn | 0142-9612 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/188456 | - |
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.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Elsevier Science | - |
dc.relation.isPartOf | BIOMATERIALS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | CRISPR-Cas Systems / genetics | - |
dc.subject.MESH | Endothelial Cells / metabolism | - |
dc.subject.MESH | Hemophilia A* / genetics | - |
dc.subject.MESH | Hemophilia A* / metabolism | - |
dc.subject.MESH | Hemophilia A* / therapy | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Induced Pluripotent Stem Cells* / metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Organoids / metabolism | - |
dc.title | Therapeutic correction of hemophilia A using 2D endothelial cells and multicellular 3D organoids derived from CRISPR/Cas9-engineered patient iPSCs | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Physiology (생리학교실) | - |
dc.contributor.googleauthor | Jeong Sang Son | - |
dc.contributor.googleauthor | Chul-Yong Park | - |
dc.contributor.googleauthor | Gyunggyu Lee | - |
dc.contributor.googleauthor | Ji Young Park | - |
dc.contributor.googleauthor | Hyo Jin Kim | - |
dc.contributor.googleauthor | Gyeongmin Kim | - |
dc.contributor.googleauthor | Kyun Yoo Chi | - |
dc.contributor.googleauthor | Dong-Hun Woo | - |
dc.contributor.googleauthor | Choongseong Han | - |
dc.contributor.googleauthor | Sang Kyum Kim | - |
dc.contributor.googleauthor | Han-Jin Park | - |
dc.contributor.googleauthor | Dong-Wook Kim | - |
dc.contributor.googleauthor | Jong-Hoon Kim | - |
dc.identifier.doi | 10.1016/j.biomaterials.2022.121429 | - |
dc.contributor.localId | A00406 | - |
dc.contributor.localId | A01719 | - |
dc.relation.journalcode | J00312 | - |
dc.identifier.eissn | 1878-5905 | - |
dc.identifier.pmid | 35217482 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0142961222000680 | - |
dc.subject.keyword | Endothelial cells | - |
dc.subject.keyword | Genome-editing | - |
dc.subject.keyword | Hemophilia A | - |
dc.subject.keyword | Induced pluripotent stem cells | - |
dc.contributor.alternativeName | Kim, Dong Wook | - |
dc.contributor.affiliatedAuthor | 김동욱 | - |
dc.contributor.affiliatedAuthor | 박철용 | - |
dc.citation.volume | 283 | - |
dc.citation.startPage | 121429 | - |
dc.identifier.bibliographicCitation | BIOMATERIALS, Vol.283 : 121429, 2022-04 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.