In Vitro Modeling of Atherosclerosis Using iPSC-Derived Blood Vessel Organoids.

Autor: Kong D; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Ryu JC; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; Institute of Bio and Nano Convergence, Biogo Co., LTD, Seoul, 08826, Republic of Korea., Shin N; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Lee SE; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Kim NG; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Kim HY; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Kim MJ; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Choi J; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Kim DH; Department of Biotechnology, Sungshin Women's University, Seoul, 01133, Republic of Korea., Kang KS; Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.; The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2025 Jan; Vol. 14 (1), pp. e2400919. Date of Electronic Publication: 2024 Nov 24.
DOI: 10.1002/adhm.202400919
Abstrakt: As modeling of atherosclerosis requires recapitulating complex interactions with vasculature and immune cells, previous in vitro models have limitations due to their insufficient 3D vascular structures. However, induced pluripotent stem cell-derived blood vessel organoids (BVOs) are applicable for modeling vascular diseases, containing multiple cell types, including endothelial and vascular smooth muscle cells self-assembled into a blood vessel structure. Atherosclerotic BVOs with a microenvironment associated with atherogenesis, such as shear stress, low-density lipoprotein, pro-inflammatory cytokine, and monocyte co-culture are successfully developed. In atherosclerotic BVOs, representative atherosclerotic phenotypes, including endothelial dysfunction, inflammatory responses, formation of foam cells and fibrous plaque, and moreover, calcification of the plaques are observed. To verify the drug response in this model, it is treated with clinically used lovastatin and confirm phenotype attenuation. Furthermore, the therapeutic efficacy of nano-sized graphene oxides (NGOs) is evaluated on atherosclerosis. Due to their anti-inflammatory effects, NGOs effectively alleviate the pathologic lesions in atherosclerotic BVOs by promoting macrophage polarization toward M2. These results suggest that atherosclerotic BVOs are advanced in vitro models suitable for drug discovery and elucidation of therapeutic mechanisms. From the perspective of precision medicine, this platform using patient-derived BVOs can be further employed for personalized drug screening in the future.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: