Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease.

ABSTRACT:

Background and aims

Alpha-1 antitrypsin (AAT) is a product of SERPINA1 gene mainly expressed by hepatocytes. Clinically relevant mutations in the SERPINA1 gene, such as Z (Glu342Lys), results in an expression of misfolded AAT protein having high propensity to polymerize, accumulate in hepatocytes and thus to enhance a risk for hepatocyte damage and subsequent liver disease. So far, the relationship between the Z-AAT accumulation and liver cell damage remains not completely understood. We present three-dimensional organoid culture systems, as a novel tool for modeling Z-AAT-related liver diseases.

Methods

We have established liver organoids from liver biopsies of patients with homozygous (ZZ) and heterozygous (MZ) deficiency and normal (MM) genotypes of AAT. The features of t

SUBMITTER: Gomez-Mariano G 

PROVIDER: S-EPMC6994530 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature