Human hepatocytes and uses thereof

Abstract

Disclosed herein are human hepatocytes for example isolated human hepatic progenitor cells, artificial tissue or organ thereof, and kits or compositions thereof. Also disclosed herein are various methods of using a human hepatocyte disclosed herein.

What is claimed: 
     
         1 . An isolated human hepatocyte derived from a trophoblast stem cell, wherein the hepatocyte endogenously expresses one or more biomarkers selected from the group consisting of cytokeratin 8 (CK8); phosphoenolpyruvate carboxykinase 2, mitochondrial (PCK2); glycogen synthase 2 (GYS2); hepatocyte nuclear factor 6 (HNF6); alcohol dehydrogenase 1C (class I) gamma polypeptide (ADH1C); cytochrome P450 3A4 (CYP3A4); hexosaminidase A alpha polypeptide (HEXA); and any combination thereof. 
     
     
         2 . The isolated human hepatocyte of  claim 1 , wherein the isolated human hepatocyte further expresses keratin 8 (KRT8), keratin 18 (KRT18), keratin 19 (KRT19), prospero homeobox 1 (PROX1), tryptophan 2, 3-dioxygenase (TDO2), or any combination thereof. 
     
     
         3 . The isolated human hepatocyte of  claim 1 , wherein the isolated human hepatocyte endogenously expresses human leukocyte antigen G (HLA-G). 
     
     
         4 . The isolated human hepatocyte of  claim 1 , wherein the isolated human hepatocyte further expresses TGFβ1. 
     
     
         5 . The isolated human hepatocyte of  claim 1 , wherein the isolated human hepatocyte is a human hepatic progenitor cell. 
     
     
         6 . The isolated human hepatocyte of  claim 1 , wherein the isolated human hepatocyte recruits CD4+FOXP3+Treg cells. 
     
     
         7 . The isolated human hepatocyte of  claim 1 , wherein a plurality of the isolated human hepatocytes forms a tissue of a 3-dimensional structure. 
     
     
         8 . The isolated human hepatocyte of  claim 1 , wherein a plurality of the isolated human hepatocytes forms a crescent cell mass. 
     
     
         9 . A population of isolated human hepatocytes that comprises a plurality of the isolated human hepatocytes of  claim 1 , wherein the plurality of isolated human hepatocytes is present in a cluster or an aggregate. 
     
     
         10 . A kit that comprises the isolated human hepatocyte of  claim 1  and a carrier. 
     
     
         11 . A pharmaceutical composition that comprises the isolated human hepatocyte of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         12 . A method of treating a disorder of liver tissue or liver function in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of  claim 11 , whereby the disorder is treated. 
     
     
         13 . A method of screening a therapeutic compound for use in treatment or prevention of a condition, comprising:
 a. contacting the isolated human hepatocyte of  claim 1 , with the therapeutic compound; and   b. detecting an expression level of a biomarker in the isolated human hepatocyte.   
     
     
         14 . A method of producing a therapeutic protein, comprising culturing the isolated human hepatocyte of  claim 1  in a medium and extracting the therapeutic protein from the medium. 
     
     
         15 . A method of regenerating a liver, comprising applying the isolated human hepatocyte of  claim 1  to an ex vivo perfusion system to regenerate the liver. 
     
     
         16 . A cell therapy, comprising intravenously administering to a subject in need thereof a composition that comprises the isolated human hepatocyte of  claim 1 . 
     
     
         17 . A method of bioprinting, comprising applying the isolated human hepatocyte of  claim 1  to a bioprinting system. 
     
     
         18 . A method of generating a tissue scaffold, comprising culturing the isolated human hepatocyte of  claim 1  in a medium on a three-dimensional biocompatible substrate to generate the tissue scaffold. 
     
     
         19 . An artificial tissue or organ, comprising human hepatocytes that express one or more biomarkers selected from the group consisting of cytokeratin 8 (CK8);
 phosphoenolpyruvate carboxykinase 2, mitochondrial (PCK2); glycogen synthase 2 (GYS2); hepatocyte nuclear factor 6 (HNF6); alcohol dehydrogenase 1C (class I) gamma polypeptide (ADH1C); cytochrome P450 3A4 (CYP3A4); hexosaminidase A alpha   polypeptide (HEXA); and any combination thereof.   
     
     
         20 . The artificial tissue or organ of  claim 19 , wherein the human hepatocytes further express HLA-G, TGFβ1, or a combination of HLA-G and TGFβ1.