Experimental model for successful liver cell therapy by lenti ttr-yapert2 transduced hepatocytes with tamoxifen control of yap subcellular location

Mladen Yovchev, Fadi L. Jaber, Zhonglei Lu, Shachi Patel, Joseph Locker, Leslie E. Rogler, John W. Murray, Marius Sudol, Mariana D. Dabeva, Liang Zhu, David A. Shafritz

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article number19275
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 14 2016

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Tamoxifen
Cell- and Tissue-Based Therapy
Hepatocytes
Theoretical Models
Liver
Lentivirus
Prealbumin
Pathology
Growth
Proteins

ASJC Scopus subject areas

  • General

Cite this

Experimental model for successful liver cell therapy by lenti ttr-yapert2 transduced hepatocytes with tamoxifen control of yap subcellular location. / Yovchev, Mladen; Jaber, Fadi L.; Lu, Zhonglei; Patel, Shachi; Locker, Joseph; Rogler, Leslie E.; Murray, John W.; Sudol, Marius; Dabeva, Mariana D.; Zhu, Liang; Shafritz, David A.

In: Scientific Reports, Vol. 6, 19275, 14.01.2016.

Research output: Contribution to journalArticle

Yovchev, Mladen ; Jaber, Fadi L. ; Lu, Zhonglei ; Patel, Shachi ; Locker, Joseph ; Rogler, Leslie E. ; Murray, John W. ; Sudol, Marius ; Dabeva, Mariana D. ; Zhu, Liang ; Shafritz, David A. / Experimental model for successful liver cell therapy by lenti ttr-yapert2 transduced hepatocytes with tamoxifen control of yap subcellular location. In: Scientific Reports. 2016 ; Vol. 6.
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AU - Lu, Zhonglei

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AU - Locker, Joseph

AU - Rogler, Leslie E.

AU - Murray, John W.

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