Generation of Liver Disease-Specific Induced Pluripotent Stem Cells Along with Efficient Differentiation to Functional Hepatocyte-Like Cells
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The availability of disease-specific induced pluripotent stem cells (iPSCs) offers a unique opportunity for studying and modeling the effects of specific gene defects on human liver development in vitro and for testing small molecules or other potential therapies for relevant liver disorders. Here we report, for the first time, the derivation of iPSCs by the retroviral transduction of Yamanaka’s factors in serum and feeder-free culture conditions from liver-specific patients with tyrosinemia, glycogen storage disease, progressive familial hereditary cholestasis, and two siblings with Crigler-Najjar syndrome. Furthermore, they were differentiated into functional hepatocyte-like cells efficiently. These iPSCs possessed properties of human embryonic stem cells (hESCs) and were successfully differentiated into three lineages that resembled hESC morphology, passaging, surface and pluripotency markers, normal karyotype, DNA methylation, and differentiation. The hepatic lineage-directed differentiation showed that the iPSC-derived hepatic cells expressed hepatocyte-specific markers. Their functionality was confirmed by glycogen and lipid storage activity, secretion of albumin, alpha-fetoprotein, and urea, CYP450 metabolic activity, as well as LDL and indocyanin green uptake. Our results provide proof of principal that human liver-disease specific iPSCs present an exciting potential venue toward cell-based therapeutics, drug metabolism, human liver development and disease models for liver failure disorders.
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- Generation of Liver Disease-Specific Induced Pluripotent Stem Cells Along with Efficient Differentiation to Functional Hepatocyte-Like Cells
Stem Cell Reviews and Reports
Volume 6, Issue 4 , pp 622-632
- Cover Date
- Print ISSN
- Online ISSN
- Humana Press Inc
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- Human induced pluripotent stem cells
- Liver disease
- Industry Sectors
- Author Affiliations
- 1. Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran
- 2. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
- 3. Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
- 4. Department of Regenerative Biomedicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- 5. Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
- 6. Department of Molecular Systems Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- 7. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran