Liver organoids as a primary human model to study HBV-mediated Hepatocellular carcinoma. A review

Sharma, Simran; Rawal, Preety; Kaur, Simranpreet; Puria, Rekha

doi:10.1016/j.yexcr.2023.113618

Cited by 2 publications

(1 citation statement)

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“…Studying liver involvement from patient samples is limited, mainly because it is a rare disease, but on the other hand, because of the difficulty of maintaining cultures of primary human hepatocytes. Currently, the establishment of 3D organoid cultures is being used as a model for the study of diseases [ 19 , 22 , 23 ]. The establishment of a liver organoid culture from a Niemann–Pick type B patient and a healthy control allowed us to characterize key features of the liver disease.…”

Section: Discussionmentioning

confidence: 99%

Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis

Gomez-Mariano,

Perez-Luz,

Ramos-Del Saz

et al. 2023

IJMS

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Acid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease type A (NPA), type B (NPB) and type A/B (NPA/B), is a rare lysosomal storage disease characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, in severe cases, neurons. A disease model was established by generating liver organoids from a NPB patient carrying the p.Arg610del variant in the SMPD1 gene. Liver organoids were characterized by transcriptomic and lipidomic analysis. We observed altered lipid homeostasis in the patient-derived organoids showing the predictable increase in sphingomyelin (SM), together with cholesterol esters (CE) and triacylglycerides (TAG), and a reduction in phosphatidylcholine (PC) and cardiolipins (CL). Analysis of lysosomal gene expression pointed to 24 downregulated genes, including SMPD1, and 26 upregulated genes that reflect the lysosomal stress typical of the disease. Altered genes revealed reduced expression of enzymes that could be involved in the accumulation in the hepatocytes of sphyngoglycolipids and glycoproteins, as well as upregulated genes coding for different glycosidases and cathepsins. Lipidic and transcriptome changes support the use of hepatic organoids as ideal models for ASMD investigation.

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Section: Discussionmentioning

confidence: 99%