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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 |
Appears in Collections: | Staff Publications Elements |
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