Drug-induced phospholipidosis in hepatic cells derived from human skin-derived precursors
Scope of the method
- Human health
- Translational - Applied Research
- In vitro - Ex vivo
- Human derived cells / tissues / organs
Description
- toxicology
- in vitro
- drug testing
- Intracellular lipids
- phospholipids
- Phospholipidosis
- amiodarone
- hepatic differentiation
- Hepatotoxicity
- skin-derived precursors
- skin stem cells
Drug-induced phospholipidosis (DIPL) is a metabolic disorder characterized by an excessive intracellular accumulation of phospholipids caused by cationic drugs. Hepatic cells derived from human skin are evaluated as an in vitro model to investigate DIPL and its mechanisms. Human skin stem cells (hSKP) are isolated, under informed consent, from human circumcised foreskin samples of young boys and hSKP are differentiated for 24 days to obtain hepatic-like cells (hSKP-HPC), as previously described. hSKP-HPC are exposed to amiodarone, a drug known to induce phospholipidosis in humans. Upon exposure to amiodarone for 24, 48, 72h, hSKP-HPC retain intracellular phospholipids, form lamellar bodies and show alterations at the gene expression level. Overall, these findings prove that hSKP-HPC might contribute to setting up an accurate in vitro platform for hepatotoxicity testing.
- Laminar air flow;
- Flow cytometry;
- Transmission electron microscopy;
- Reverse transcriptase-polymerase chain reaction (qPCR) reagents.
- History of use
Pros, cons & Future potential
- Applicability of hSKP-HPC for the quick assessment of drug-induced phospholipidosis in vitro;
- Different human donors can be tested to assess toxicity.
In vitro toxicity testing in the drug development process
References, associated documents and other information
W. H. Halliwell, “Amphiphilic Drug-Induced Phospholipidosis,” Toxicol. Pathol., vol. 25, no. 1, pp. 53–60, 1997. [2] R. M. Rodrigues et al., “Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals.,” Stem Cells Dev., vol. 23, no. 1, pp. 44–55, 2014
Organisations
Vrije Universiteit Brussel (VUB)Pharmaceutical and Pharmacological Sciences
In Vitro Toxicology and Dermato-Cosmetology
Belgium