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A long-term hepatocyte culture maintaining liver-specific functions is very essential for both basic research and the development of bioartificial liver devices in clinical application. However, primary hepatocytes rapidly lose their proliferation and hepatic functions over a few days in culture. This work is to establish an ornithine transcarbamylase deficiency (OTCD) patient-derived primary human hepatocyte (OTCD-PHH) culture with hepatic functions for providing an in vitro cell model. Liver tissue from an infant with OTCD was dispersed into single cells. The cells were cultured using conditional reprogramming. To characterize the cells, we assessed activities and mRNA expression of CYP3A4, 1A1, 2C9, as well as albumin and urea secretion. We found that the OCTD-PHH can be subpassaged for more than 15 passages. The cells do not express mRNA of fibroblast-specific maker, whereas they highly express markers of epithelial cells and hepatocytes. In addition, the OTCD-PHH retain native CYP3A4, 1A1, 2C9 activities and albumin secretion function at early passages. The OTCD-PHH at passages 2, 6, 9 and 13 have identical DNA fingerprint as the original tissue. Furthermore, under 3D culture environment, low urea production and hepatocyte marker staining of the OTCD-PHH were detected. The established OTCD-PHH maintain liver-specific functions at early passages and can be long-term cultured in vitro. We believe the established long-term OTCD-PHH culture is highly relevant to study liver diseases, particularly in infants with OTCD.
This article was published in the following journal.
Name: Experimental cell research
Ornithine transcarbamylase deficiency (OTCD) is a common metabolic disease of urea circulation disorder. We reported the clinical, brain imaging and genetic characteristics of 2 cases with OTCD. The p...
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Determine the long-term safety of DTX301 following a single intravenous (IV) dose in adults with late-onset ornithine transcarbamylase (OTC) deficiency.
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A urea cycle enzyme that catalyzes the formation of orthophosphate and L-citrulline (CITRULLINE) from CARBAMOYL PHOSPHATE and L-ornithine (ORNITHINE). Deficiency of this enzyme may be transmitted as an X-linked trait. EC 188.8.131.52.
A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ornithine (ORNITHINE) and urea. Deficiency of this enzyme causes HYPERARGININEMIA. EC 184.108.40.206.
An inherited urea cycle disorder associated with deficiency of the enzyme ORNITHINE CARBAMOYLTRANSFERASE, transmitted as an X-linked trait and featuring elevations of amino acids and ammonia in the serum. Clinical features, which are more prominent in males, include seizures, behavioral alterations, episodic vomiting, lethargy, and coma. (Menkes, Textbook of Child Neurology, 5th ed, pp49-50)
A hepatocyte nuclear factor that is closely related to HEPATOCYTE NUCLEAR FACTOR 1-ALPHA but is only weakly expressed in the LIVER. Mutations in hepatocyte nuclear factor 1-beta are associated with renal CYSTS and MATURITY-ONSET DIABETES MELLITUS type 5.
A transcription factor that regulates the expression of a large set of hepatic proteins including SERUM ALBUMIN; beta-fibrinogen; and ALPHA 1-ANTITRYPSIN. It is composed of hetero- or homo-dimers of HEPATOCYTE NUCLEAR FACTOR 1-ALPHA and HEPATOCYTE NUCLEAR FACTOR 1-BETA.
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