US 12,252,712 B2
Use of engineered liver tissue constructs for modeling liver disorders
Deborah Lynn Greene Nguyen, San Diego, CA (US); Dwayne E. Carter, San Diego, CA (US); Rhiannon Hardwick, San Diego, CA (US); Alice Chen Walters, San Diego, CA (US); Sharon C. Presnell, Poway, CA (US); Chirag B. Khatiwala, San Diego, CA (US); and Rami Nasrallah, San Diego, CA (US)
Assigned to Organovo, Inc., San Diego, CA (US)
Appl. No. 16/500,521
Filed by Deborah Lynn Greene Nguyen, San Diego, CA (US); Dwayne E. Carter, San Diego, CA (US); Rhiannon Hardwick, San Diego, CA (US); Alice Chen Walters, San Diego, CA (US); Sharon C. Presnell, Poway, CA (US); Chirag B. Khatiwala, San Diego, CA (US); and Rami Nasrallah, San Diego, CA (US)
PCT Filed Apr. 3, 2018, PCT No. PCT/US2018/025960
§ 371(c)(1), (2) Date Oct. 3, 2019,
PCT Pub. No. WO2018/187380, PCT Pub. Date Oct. 11, 2018.
Claims priority of provisional application 62/480,961, filed on Apr. 3, 2017.
Prior Publication US 2020/0115682 A1, Apr. 16, 2020
Int. Cl. C12N 5/071 (2010.01); G01N 33/50 (2006.01); G01N 33/68 (2006.01); G09B 23/30 (2006.01)
CPC C12N 5/0671 (2013.01) [G01N 33/5082 (2013.01); G01N 33/6893 (2013.01); G09B 23/306 (2013.01); C12N 2502/1157 (2013.01); C12N 2502/1305 (2013.01); C12N 2502/14 (2013.01); C12N 2503/04 (2013.01); C12N 2513/00 (2013.01); C12N 2533/00 (2013.01); C12N 2535/00 (2013.01); G01N 2800/085 (2013.01); G01N 2800/52 (2013.01)] 15 Claims
 
1. A culture comprising a three-dimensional, engineered, bioprinted, biological liver tissue construct and a culture medium, wherein the liver tissue construct comprises parenchymal cells and non-parenchymal cells, the parenchymal cells comprising hepatocytes and the non-parenchymal cells comprising endothelial cells and hepatic stellate cells, and wherein the culture medium comprises: a palmitic acid, an oleic acid, or a combination thereof in a concentration that is capable of inducing a nonalcoholic steatohepatitis (NASH) phenotype in the liver tissue construct, and wherein the liver tissue construct comprises the NASH phenotype comprising a lipid accumulation, a hepatocellular ballooning, a macrovesicular steatosis, and a histological fibrosis induced by the palmitic acid, oleic acid, or combination thereof.