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In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease
Name
nihms954212.pdf
Description
Accepted version
Size
3.84 MB
Format
Adobe PDF
Checksum (MD5)
f372732d0364c6b4f85a0c499f6dfdb3
Author(s)
Stevens, Kelly R.
Scull, Margaret A.
Ramanan, Vyas
Fortin, Chelsea L.
Chaturvedi, Ritika R.
Knouse, Kristin Ann
Xiao, Jing W.
Fung, Canny
Mirabella, Teodelinda
Chen, Amanda X.
Date Issued
July 19, 2017
Journal
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Stevens, Kelly R., Scull, Margaret A., Ramanan, Vyas, Fortin, Chelsea L., Chaturvedi, Ritika R. et al. 2017. "In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease." Science Translational Medicine, 9 (399).
Version
Author's final manuscript
Abstract
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Control of both tissue architecture and scale is a fundamental translational roadblock in tissue engineering. An experimental framework that enables investigation into how architecture and scaling may be coupled is needed. We fabricated a structurally organized engineered tissue unit that expanded in response to regenerative cues after implantation into mice with liver injury. Specifically, we found that tissues containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers. There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins. Histologically, we observed the emergence of characteristic liver stereotypical microstructures mediated by coordinated growth of hepatocytes in close juxtaposition with a perfused vasculature. We demonstrated the utility of this system for probing the impact of multicellular geometric architecture on tissue expansion in response to liver injury. This approach is a hybrid strategy that harnesses both biology and engineering to more efficiently deploy a limited cell mass after implantation.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
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.
Persistent DSpace Link
DOI of Published Version
http://dx.doi.org/10.1126/scitranslmed.aah5505
