Research ArticleTissue Engineering

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

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Science Translational Medicine  19 Jul 2017:
Vol. 9, Issue 399, eaah5505
DOI: 10.1126/scitranslmed.aah5505

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Tissue seeds blossom after transplant

There is an enormous clinical need for liver transplant tissue. Bioengineered livers might ultimately be used as a bridge to or alternative for whole organ transplantation. In new work, Stevens et al. fabricated human artificial liver “seeds” in biomaterials that were able to grow and expand after implantation into mice in response to liver injury. After growth, the human artificial liver seeds were able to carry out normal liver functions such as production of human proteins like transferrin and albumin. This study suggests that implanted engineered tissue seeds should be able to expand in response to the body’s own repair signals.

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.

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