Embolization-on-a-chip: novel vascularized liver tumor model for evaluation of cellular and cytokine response to embolic agents.
| Title: | Embolization-on-a-chip: novel vascularized liver tumor model for evaluation of cellular and cytokine response to embolic agents. |
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| Authors: | Nguyen HT; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Tirpakova Z; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Department of Biology and Physiology, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 04181 Kosice, Slovakia.; Peirsman A; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Plastic, Reconstructive and Aesthetic Surgery, Ghent University Hospital, Ghent 9000, Belgium.; Maity S; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Falcone N; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Kawakita S; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Jeon K; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Khorsandi D; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Rashad A; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Department of Clinical Dentistry, University of Bergen, Bergen 5009, Norway.; Farhadi N; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Mandal K; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Ermis M; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Herculano RD; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; São Paulo State University, Bioengineering & Biomaterials Group, School of Pharmaceutical Sciences, Zip Code: 14800-903 Araraquara, SP, Brazil.; Najafabadi AH; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Dokmeci MR; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; De Barros NR; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; National Laboratory of Bioscience, National Center of Research in Energy and Materials, Campinas 13083-100, Brazil.; Khademhosseini A; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America.; Jucaud V; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, United States of America. |
| Source: | Biofabrication [Biofabrication] 2025 Sep 29; Vol. 17 (4). Date of Electronic Publication: 2025 Sep 29. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: IOP Pub Country of Publication: England NLM ID: 101521964 Publication Model: Electronic Cited Medium: Internet ISSN: 1758-5090 (Electronic) Linking ISSN: 17585082 NLM ISO Abbreviation: Biofabrication Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Bristol : IOP Pub., 2009- |
| MeSH Terms: | Liver Neoplasms*/blood supply ; Liver Neoplasms*/pathology ; Liver Neoplasms*/metabolism ; Liver Neoplasms*/therapy ; Cytokines*/metabolism ; Carcinoma, Hepatocellular*/blood supply ; Carcinoma, Hepatocellular*/pathology ; Lab-On-A-Chip Devices* ; Embolization, Therapeutic*; Hydrogels/chemistry ; Cell Survival/drug effects ; Tumor Microenvironment/drug effects ; Humans ; Hep G2 Cells |
| Abstract: | Blood vessel embolization is a well-established treatment modality for liver cancer. Novel shear-thinning hydrogels (STH) have been developed to address the need for safer and more effective local delivery of embolic agents and therapeutics. However, embolization therapies are currently optimized in animal models, which often differ from humans at the cellular, tissue, and organ levels. We aim to evaluate the efficacy of novel embolic agents such as STH using a human-relevantin vitromodel that recapitulates human hepatocellular carcinoma capillary networks. A vascularized human liver-tumor-on-a-chip model was developed to assess embolic agent performance. The effects of drug-eluting STH (DESTH) on tumor cell viability, surface marker expression, vasculature morphology, and cytokine responses were evaluated. To study the effects of embolization on microvasculature morphology independent of the chemotherapy compound, we evaluated the effect of different drug-free embolic agents on the vascular tumor microenvironment under flow conditions. DESTH treatment induced tumor cell death, downregulated the expression of epithelial cell adhesion molecules in HepG2, increased levels of cytokines such as interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor, and vascular endothelial growth factor, and decreased albumin secretion. Furthermore, different embolic agents exert distinct effects on microvascular morphology, with STH causing complete regression of the microvascular networks. This vascularized liver tumor-on-a-chip model enables human-relevant, real-time assessment of embolic agent efficacy and vascular response and can be applied for the development of innovative and effective embolization therapies for liver cancer.; (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.) |
| Grant Information: | R01 AI183529 United States AI NIAID NIH HHS; R01 DK130566 United States DK NIDDK NIH HHS; R21 EB034423 United States EB NIBIB NIH HHS |
| Contributed Indexing: | Keywords: hepatocellular carcinoma; microfluidics; microphysiological systems; microvasculature; tissue engineering; transcatheter arterial chemoembolization; vascularized tumor models |
| Molecular Sequence: | figshare https://doi.org/10.6084/m9.figshare.28599905 |
| Substance Nomenclature: | 0 (Cytokines); 0 (Hydrogels) |
| Entry Date(s): | Date Created: 20250814 Date Completed: 20250929 Latest Revision: 20260513 |
| Update Code: | 20260513 |
| DOI: | 10.1088/1758-5090/adfbc3 |
| PMID: | 40812355 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural