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
AUTHORS (6)
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.
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CITATIONS (16)
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