Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions

• DOI: 10.1093/stmcls/sxac090
• Publication Date: 2022-12-27T10:12:02Z
• Authors: Yun Weng; Simon Han; Maria T Sekyi; Tao Su; Aras N Mattis; Tammy T Chang
• Keywords: Adult; 0301 basic medicine; 570; Technology; Biomedical and clinical sciences; induced pluripotent stem cells; Medical Biotechnology; Chronic Liver Disease and Cirrhosis; Immunology; Induced Pluripotent Stem Cells; Regenerative Medicine; liver; Medical and Health Sciences; Oral and gastrointestinal; Embryonic Stem Cells/Induced Pluripotent Stem Cells; 03 medical and health sciences; Matrigel; Humans; RNA-Seq; organoids; Biomedical and Clinical Sciences; Stem Cell Research - Induced Pluripotent Stem Cell - Human; Stem Cell Research - Induced Pluripotent Stem Cell; 5.2 Cellular and gene therapies; Liver Disease; Cell Differentiation; self-assembly; Biological Sciences; Stem Cell Research; microgravity; 3. Good health; Organoids; Biological sciences; Liver; Hepatocytes; Digestive Diseases; Biotechnology

AbstractHuman induced pluripotent stem cell (iPSC)-derived liver organoids serve as models of organogenesis, disease, drug screening, and regenerative medicine. Prevailing methods for generating organoids rely on Matrigel, whose batch-to-batch variability and xenogeneic source pose challenges to mechanistic research and translation to human clinical therapy. In this report, we demonstrate that self-assembled Matrigel-free iPSC-derived organoids developed in rotating wall vessels (RWVs) exhibit greater hepatocyte-specific functions than organoids formed on Matrigel. We show that RWVs produce highly functional liver organoids in part by eliminating the need for Matrigel, which has adverse effects on hepatic lineage differentiation. RWV liver organoids sustain durable function over long-term culture and express a range of mature functional genes at levels comparable to adult human liver, while retaining some fetal features. Our results indicate that RWVs provide a simple and high-throughput way to generate Matrigel-free liver organoids suitable for research and clinical applications.