아주대학교

목차

1. INTRODUCTION 1
1.1 Atherosclerosis 1
1.2 Limitations of current therapeutic strategies for atherosclerosis 2
1.3 Macrophages in atherosclerosis 3
1.4 iPSC-derived macrophages as a therapeutic platform 4
1.5 Organoid-based disease modeling for atherosclerosis 4
1.6 Objectives of this study 5
2. MATERIALS and METHODS 6
2.1 Generation and polarization of iPSC-derived macrophages 6
2.2 Phenotypic characterization of iMac subtypes 7
2.3 Phagocytosis assay 8
2.4 Evaluation of lipid metabolism 8
2.5 RNA sequencing and transcriptomic analysis 9
2.6 Generation of atherosclerosis-like BVOs 10
2.7 Co-culture of iMacs with atherosclerosis-like BVOs 11
2.8 Quantification of iMac accumulation within atherosclerosis-like BVOs 11
2.9 Immunohistochemistry 12
2.10 Oil Red O staining 12
2.11 Transcriptomic network and regulatory analysis 13
2.12 Reactome pathway enrichment analysis 14
2.13 Statistical analysis 14
3. RESULTS 20
3.1. Differentiation of iPSCs into macrophages establishes a reproducible iMac platform 20
3.2 Cytokine-directed polarization generates distinct macrophage subtypes 23
3.3 Polarized iMacs exhibit subtype-specific functional characteristics 25
3.4 Transcriptomic profiling reveals subtype-specific transcriptional divergence 28
3.5 Establishment of iPSC-derived atherosclerosis-like BVOs 33
3.6 Polarized iMacs exhibit differential infiltration and interaction within BVOs 36
3.7 Regenerative iMacs modulate vascular remodeling, lipid accumulation, and inflammatory response in organoids 38
3.8 Network analysis defines three-pillar regenerative macrophage programs 41
3.9 Polarization phenotypes are conserved across independent iPSC lines 45
3.10 Allogeneic regenerative iMacs retain therapeutic efficacy in organoid models 47
4. CONCLUSION 49
REFERENCES 51
ABSTRACT IN KOREAN 55