In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease. Academic Article uri icon

Overview

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.

publication date

  • July 19, 2017

Research

keywords

  • Liver
  • Liver Diseases

Identity

PubMed Central ID

  • PMC5896001

Scopus Document Identifier

  • 85025444300

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.aah5505

PubMed ID

  • 28724577

Additional Document Info

volume

  • 9

issue

  • 399