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The reconstituted 'humanized liver' in TK-NOG mice is mature and functional.

Abstract：

:To overcome the limitations of existing models, we developed a novel experimental in vivo platform for replacing mouse liver with functioning human liver tissue. To do this, a herpes simplex virus type 1 thymidine kinase (HSVtk) transgene was expressed within the liver of highly immunodeficient NOG mice (TK-NOG). Mouse liver cells expressing this transgene were ablated after a brief exposure to a non-toxic dose of ganciclovir (GCV), and transplanted human liver cells are stably maintained within the liver (humanized TK-NOG) without exogenous drug. The reconstituted liver was shown to be a mature and functioning "human organ" that had zonal position-specific enzyme expression and a global gene expression pattern representative of mature human liver; and could generate a human-specific profile of drug metabolism. The 'humanized liver' could be stably maintained in these mice with a high level of synthetic function for a prolonged period (8 months). This novel in vivo system provides an optimized platform for studying human liver physiology, including drug metabolism, toxicology, or liver regeneration.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hasegawa M,Kawai K,Mitsui T,Taniguchi K,Monnai M,Wakui M,Ito M,Suematsu M,Peltz G,Nakamura M,Suemizu H

doi

10.1016/j.bbrc.2011.01.042

subject

Has Abstract

pub_date

2011-02-18 00:00:00

pages

405-10

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)00061-1

journal_volume

405

pub_type

杂志文章

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