ORCID Profile
0000-0002-5071-6563
Current Organisation
Medical University of South Carolina
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Publisher: Springer Science and Business Media LLC
Date: 07-09-2010
DOI: 10.1007/S12015-010-9189-3
Abstract: 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.
Publisher: Springer Science and Business Media LLC
Date: 18-12-2012
DOI: 10.1007/S12033-012-9635-3
Abstract: The generation of human induced pluripotent stem cells (hiPSCs) from an in idual 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.
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.JHEP.2010.05.009
Abstract: Stem cell transplantation has been proposed as an attractive alternative approach to restore liver mass and function. Recent progress has been reported on the generation of induced pluripotent stem (iPS) cells from somatic cells. Human-iPS cells can be differentiated towards the hepatic lineage which presents possibilities for improving research on diseases, drug development, tissue engineering, the development of bio-artificial livers, and a foundation for producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. This focused review will discuss how human iPS cell advances are likely to have an impact on hepatology.
Publisher: Oxford University Press (OUP)
Date: 16-11-2011
DOI: 10.1002/STEM.760
Abstract: A major goal of regenerative medicine is to produce cells to participate in the generation, maintenance, and repair of tissues that are damaged by disease, aging, or trauma, such that function is restored. The establishment of induced pluripotent stem cells, followed by directed differentiation, offers a powerful strategy for producing patient-specific therapies. Given how laborious and lengthy this process can be, the conversion of somatic cells into lineage-specific stem rogenitor cells in one step, without going back to, or through, a pluripotent stage, has opened up tremendous opportunities for regenerative medicine. However, there are a number of obstacles to overcome before these cells can be widely considered for clinical applications. Here, we focus on induced transdifferentiation strategies to convert mature somatic cells to other mature cell types or progenitors, and we summarize the challenges that need to be met if the potential applications of transdifferentiation technology are to be achieved.
Location: Iran (Islamic Republic of)
Location: United States of America
Location: Iran (Islamic Republic of)
Location: Iran (Islamic Republic of)
No related grants have been discovered for Behshad Pournasr.