University of Cincinnati researchers have successfully bioengineered human live organoids that faithfully mimic key features of fatal liver disease in the laboratory. This allowed them to uncover underlying disease biology in the organoids and test a potential therapy that in preclinical lab tests reversed an often-fatal childhood condition called Wolman disease.
It was a collaboration of researchers at Cincinnati Children’s, the Institute of Research at Tokyo Medical and Dental University (TMDU) in Japan and researchers at four other institutions in Japan and the United States.
With findings published in Cell Metabolism, the Cincinnati researchers’ study overcomes major hurdles to unraveling the molecular mysteries of liver diseases and finding desperately needed therapies. It also leads to personalized methods to study inflammation and fibrosis in liver disease that match the unique genetics and biology of individual patients.
Investigator Takanori Takebe, MD, lead study investigator and a physician at Cincinnati Children’s Center of Stem Cell and Organoid Medicine (CuSTOM) reports, “although current human organoid systems can recreate organ architecture in living lab organisms like mice, they fail to capture the complex pathologies of inflammation and fibrosis in liver disease.”
Takebe continued, “we developed a reproducible method to bioengineer complex, multicellular human liver organoid using pluripotent stem cells derived from healthy human donors and those with liver diseases.” He said, “These organoids generate different types of liver cells like hepatocytes, stellate, and Kupffer-like cells, and they accurately recreate the lab inflammation, fibrosis and other features of liver disease.”
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Takanori Takebe, MD, lead study investigator and a physician at Cincinnati Children’s Center of Stem Cell and Organoid Medicine (CuSTOM)