Liver organoid compositions and methods of making and using same

An organoid, organoid technology, applied in the field of liver organoid composition and its preparation and use

Pending Publication Date: 2020-03-24
CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Clinical trials in a dish using human stem cells remain 'hype' despite gradual advances in human hepatocyte differentiation methods from pluripotent stem cells (PSCs)

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  • Liver organoid compositions and methods of making and using same
  • Liver organoid compositions and methods of making and using same
  • Liver organoid compositions and methods of making and using same

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[0060] In the present study, Applicants tested bile transport activity using fluorescein diacetate, which is excreted across the canalicular membrane into the bile canalicular network by MRP2 (Tian et al., 2004). Troglitazone and cyclosporine have previously been reported to inhibit MRP2 (Chang et al., 2013; Lechner et al., 2010). Furthermore, the efflux transporter MRP2 mediates the export of bosentan (Fahrmayr et al., 2013). Although the inhibitory effect of nefazodone on MRP2 has not been reported, the mitochondrial stress of nefazodone may be related to the reduction of bile transport activity, as is the efflux of fluorescein diacetate, because MRP2 is an ATP-dependent bile Salt transporter for canalicular excretion of bile acids in hepatocytes.

[0061] Preclinical testing of compounds at risk for drug-induced liver injury (DILI) remains a major challenge in drug development, highlighting the need for predictive human systems. Here, applicants developed a human liver or...

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Abstract

The present invention discloses methods of inducing formation of a liver organoid from precursor cells, such as iPSC cells. The disclosed liver organoids may be used for screening for a serious adverse event (SAE), such as liver failure and / or drug induced liver injury (DILI), and / or drug toxicity. The disclosed liver organoids may also be used to treat an individual having liver damage, or for identifying a preferred therapeutic agent.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to and benefit of US Provisional Patent Application 62 / 517,414, filed June 9, 2017, the contents of each of which are incorporated by reference in their entirety for all purposes. Background technique [0003] The liver is a vital organ that provides many vital metabolic functions for life, such as detoxification of exogenous compounds and coagulation of blood, and production of lipids, proteins, ammonium and bile. In vitro reconstruction of a patient's liver could offer applications including regenerative therapy, drug discovery, and drug toxicity studies. Existing methods using hepatocytes exhibit extremely poor functionality, mainly due to the lack of necessary anatomical structures, which limits their practical application in the pharmaceutical industry. [0004] Billions of dollars are lost annually to drug development in the pharmaceutical industry due to the failure of drug candi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/074C12N5/0789C12N5/095
CPCC12N5/0671C12N2501/119C12N2501/12C12N2501/155C12N2501/16C12N2501/237C12N2501/385C12N2501/39C12N2501/999C12N2503/02C12N2506/45C12N2533/90
Inventor 武部贵则筱泽忠纮小池博之木村昌树
Owner CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
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