Faculty Collaboration Database

Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver. Sci Rep 2021 Jun 11;11(1):12386

Date

06/13/2021

Pubmed ID

34117281

Pubmed Central ID

PMC8196029

DOI

10.1038/s41598-021-90510-1

Scopus ID

2-s2.0-85107825189 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

Parenteral nutrition-associated cholestasis (PNAC) significantly limits the safety of intravenous parenteral nutrition (PN). Critically ill infants are highly vulnerable to PNAC-related morbidity and mortality, however the impact of hepatic immaturity on PNAC is poorly understood. We examined developmental differences between fetal/infant and adult livers, and used human induced pluripotent stem cell-derived hepatocyte-like cells (iHLC) to gain insights into the contribution of development to altered sterol metabolism and PNAC. We used RNA-sequencing and computational techniques to compare gene expression patterns in human fetal/infant livers, adult liver, and iHLC. We identified distinct gene expression profiles between the human feta/infant livers compared to adult liver, and close resemblance of iHLC to human developing livers. Compared to adult, both developing livers and iHLC had significant downregulation of xenobiotic, bile acid, and fatty acid metabolism; and lower expression of the sterol metabolizing gene ABCG8. When challenged with stigmasterol, a plant sterol found in intravenous soy lipids, lipid accumulation was significantly higher in iHLC compared to adult-derived HepG2 cells. Our findings provide insights into altered bile acid and lipid metabolizing processes in the immature human liver, and support the use of iHLC as a relevant model system of developing liver to study lipid metabolism and PNAC.

Author List

Nghiem-Rao TH, Pfeifer C, Asuncion M, Nord J, Schill D, Pulakanti K, Patel SB, Cirillo LA, Rao S

Authors

Lisa A. Cirillo PhD Assistant Dean, Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
T Hang Nghiem-Rao MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cholestasis
Female
Hepatocytes
Humans
Induced Pluripotent Stem Cells
Infant, Newborn
Liver
Male
Parenteral Nutrition