Biomaterials. 2026;325:123606.
Directed differentiation of human mesenchymal stromal cells into functional endothelial cells having IKAROS-mediated immune tolerance properties.
제1저자 한정규, 이해나, 신다솜 · 교신저자 김효수, 김종일
소속 (8)
- Department of Internal Medicine, Seoul National University College of Medicine, South Korea; Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, South Korea.
- Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, South Korea.
- Genomic Medicine Institute, Medical Research Center, Seoul National University, South Korea; Department of Biomedical Sciences, Seoul National University Graduate School, South Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, South Korea.
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Cancer Research Institute, Seoul National University, South Korea; Sensory Organ Research Institute, Seoul National University Medical Research Center, South Korea.
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, South Korea.
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, South Korea; School of Mechanical Engineering, Korea University, South Korea; Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea.
- Genomic Medicine Institute, Medical Research Center, Seoul National University, South Korea; Department of Biomedical Sciences, Seoul National University Graduate School, South Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, South Korea. Electronic address: jongil@snu.ac.kr.
- Department of Internal Medicine, Seoul National University College of Medicine, South Korea; Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, South Korea. Electronic address: hyosoo@snu.ac.kr.
Abstract
We report an efficient method for the directed differentiation of mesenchymal stromal cells derived from embryonic stem cells (EMSCs) into functional endothelial cells (EC), addressing the challenges of direct conversion, such as cellular senescence. We found that transduction of one transcription factor, ER71, was required for the efficient derivation of induced endothelial cells from EMSCs (MiECs). Addition of transforming growth factor-β inhibitor (SB431542), vascular endothelial growth factor, and ascorbic acid to the culture media enhanced the differentiation efficiency. After one week of the induction protocol, 75.4 ± 4.5 % of EMSCs were directly differentiated into ECs as defined by double-positivity for VE-cadherin/PECAM1. MiECs demonstrated endothelial characteristics and functions. Interestingly, the immune tolerance of MSCs was potentiated in MiECs, and were mediated by IKAROS, a direct transcriptional target of ER71. We established an efficient protocol for direct differentiation of MSCs into functional ECs with immune tolerance properties based on ER71 transduction. This technology provides the allogenic cell source for ready-to-use cell therapies for diseases or conditions requiring vascularization.
Copyright © 2025 Elsevier Ltd. All rights reserved.
Keywords
Directed differentiationEndothelial cellsIKAROSImmune toleranceMesenchymal stromal cell
Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
그 밖의 정보
- 출판 형태
- Journal Article
- 저널
- Biomaterials · eISSN 1878-5905
- 전자 출판
- 2025-08-08
- MeSH
- Humans · Mesenchymal Stem Cells* / cytology / immunology / drug effects / metabolism · Cell Differentiation* / drug effects · Endothelial Cells* / cytology / immunology / drug effects / metabolism · Ikaros Transcription Factor* / metabolism · Immune Tolerance* · Cells, Cultured
- Substances
- Ikaros Transcription Factor