Humanized mice with ectopic artificial liver tissues
Name
Bhatia-2011-July-Humanized mice with ectopic artificial liver tissues.pdf
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1.8 MB
Format
Adobe PDF
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Author(s)
Thomas, David K.
Chen, Alice
Ong, Luvena L.
Schwartz, Robert E.
Golub, Todd
Bhatia, Sangeeta N
Date Issued
July 2011
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences (PNAS)
Citation
Chen, A. A. et al. “Humanized mice with ectopic artificial liver tissues.” Proceedings of the National Academy of Sciences 108.29 (2011): 11842-11847. Web. 2 Feb. 2012.
Version
Final published version
Abstract
“Humanized” mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury but these methods have not gained widespread use due to the duration and variability of hepatocyte repopulation. In light of the significant progress that has been achieved in clinical cell transplantation through tissue engineering, we sought to develop a humanized mouse model based on the facile and ectopic implantation of a tissue-engineered human liver. These human ectopic artificial livers (HEALs) stabilize the function of cryopreserved primary human hepatocytes through juxtacrine and paracrine signals in polymeric scaffolds. In contrast to current methods, HEALs can be efficiently established in immunocompetent mice with normal liver function. Mice transplanted with HEALs exhibit humanized liver functions persistent for weeks, including synthesis of human proteins, human drug metabolism, drug–drug interaction, and drug-induced liver injury. Here, mice with HEALs are used to predict the disproportionate metabolism and toxicity of “major” human metabolites using multiple routes of administration and monitoring. These advances may enable manufacturing of reproducible in vivo models for diverse drug development and research applications.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1101791108
