Disease-corrected hepatocyte-like cells from familial hypercholesterolemia- induced pluripotent stem cells

Faranak Fattahi, Samira Asgari, Behshad Pournasr, Ali Seifinejad, Mehdi Totonchi, Adeleh Taei, Nasser Aghdami, Ghasem Hosseini Salekdeh*, Hossein Baharvand

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


The generation of human induced pluripotent stem cells (hiPSCs) from an individual patient provides a unique tool for disease modeling, drug discovery, and cell replacement therapies. Patient-specific pluripotent stem cells can be expanded in vitro and are thus suitable for genetic manipulations. To date, several genetic liver disorders have been modeled using patient-specific hiPSCs. Here, we present the generation of corrected hepatocyte-like cells (HLCs) from hiPSCs of a familial hypercholesterolemia (FH) patient with a homozygous mutation in the low-density lipoprotein receptor (LDLR) gene. We generated hiPSCs from a patient with FH with the mutated gene encoding a truncated non-functional receptor. In order to deliver normal LDLR to the defective cells, we used a plasmid vector carrying the normal receptor ORF to genetically transform the hiPSCs. The transformed cells were expanded and directed toward HLCs. Undifferentiated defective hiPSCs and HLCs differentiated from the defective hiPSCs did not have the ability to uptake labeled low-density lipoprotein (LDL) particles. The differentiated transformed hiPSCs showed LDL-uptake ability and the correction of disease phenotype as well as expressions of hepatocyte-specific markers. The functionality of differentiated cells was also confirmed by indo-cyanine green (ICG) uptake assay, PAS staining, inducible cyp450 activity, and oil red staining. These data suggest that hiPSC technology can be used for generation of disease-corrected, patient-specific HLCs with potential value for disease modeling and drug discovery as well as cell therapy applications in future.

Original languageEnglish
Pages (from-to)863-873
Number of pages11
JournalMolecular Biotechnology
Issue number3
Publication statusPublished - 1 Jul 2013
Externally publishedYes


  • Disease-specific human induced pluripotent stem cells
  • Familial hypercholesterolemia
  • Hepatocyte differentiation
  • LDLR gene therapy


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