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

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
DOI: 10.1093/stmcls/sxac090 Publication Date: 2022-12-27T10:12:02Z
ABSTRACT
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (47)
CITATIONS (16)