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Sci Transl Med. 2017 Jul 19;9(399). pii: eaah5505. doi: 10.1126/scitranslmed.aah5505.

In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease.

Author information

1
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
2
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
3
Departments of Bioengineering and Pathology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
4
Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
5
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
6
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
7
Harvard Medical School, Boston, MA 02115, USA.
8
Department of Bioengineering, Boston University, Boston, MA 02215, USA.
9
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
10
Innolign Biomedical, Natick, MA 01760, USA.
11
Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
12
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. sbhatia@mit.edu.
13
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
14
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Abstract

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.

PMID:
28724577
PMCID:
PMC5896001
DOI:
10.1126/scitranslmed.aah5505
[Indexed for MEDLINE]
Free PMC Article

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