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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Yovchev M,Jaber FL,Lu Z,Patel S,Locker J,Rogler LE,Murray JW,Sudol M,Dabeva MD,Zhu L,Shafritz DAdoi
10.1038/srep19275subject
Has Abstractpub_date
2016-01-14 00:00:00pages
19275issn
2045-2322pii
srep19275journal_volume
6pub_type
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