Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep19275
Title: Experimental model for successful liver cell therapy by lenti ttr-yapert2 transduced hepatocytes with tamoxifen control of yap subcellular location
Authors: Yovchev, M
Jaber, F.L
Lu, Z
Patel, S
Locker, J
Rogler, L.E
Murray, J.W
Sudol, M 
Dabeva, M.D
Zhu, L
Shafritz, D.A
Keywords: hybrid protein
nuclear protein
prealbumin
tamoxifen
transcription factor
YY1AP1 protein, human
animal
animal model
biological therapy
drug effects
gene expression
gene vector
genetic transduction
genetics
Lentivirinae
liver cell
liver regeneration
metabolism
promoter region
protein transport
rat
reporter gene
transplantation
Animals
Cell- and Tissue-Based Therapy
Gene Expression
Genes, Reporter
Genetic Vectors
Hepatocytes
Lentivirus
Liver Regeneration
Models, Animal
Nuclear Proteins
Prealbumin
Promoter Regions, Genetic
Protein Transport
Rats
Recombinant Fusion Proteins
Tamoxifen
Transcription Factors
Transduction, Genetic
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Yovchev, M, Jaber, F.L, Lu, Z, Patel, S, Locker, J, Rogler, L.E, Murray, J.W, Sudol, M, Dabeva, M.D, Zhu, L, Shafritz, D.A (2016). Experimental model for successful liver cell therapy by lenti ttr-yapert2 transduced hepatocytes with tamoxifen control of yap subcellular location. Scientific Reports 6 : 19275. ScholarBank@NUS Repository. https://doi.org/10.1038/srep19275
Abstract: Liver repopulation by transplanted hepatocytes has not been achieved previously in a normal liver microenvironment. Here we report that adult rat hepatocytes transduced ex vivo with a lentivirus expressing a human YapERT2 fusion protein (hYapERT2) under control of the hepatocyte-specific transthyretin (TTR) promoter repopulate normal rat liver in a tamoxifen-dependent manner. Transplanted hepatocytes expand very slowly but progressively to produce 10% repopulation at 6 months, showing clusters of mature hepatocytes that are fully integrated into hepatic parenchyma, with no evidence for dedifferentiation, dysplasia or malignant transformation. Thus, we have developed the first vector designed to regulate the growth control properties of Yap that renders it capable of producing effective cell therapy. The level of liver repopulation achieved has significant translational implications, as it is 2-3x the level required to cure many monogenic disorders of liver function that have no underlying hepatic pathology and is potentially applicable to diseases of other tissues and organs.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/175444
ISSN: 20452322
DOI: 10.1038/srep19275
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