Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets

Nat Med. 2007 Jul;13(7):880-5. doi: 10.1038/nm1576. Epub 2007 Jun 17.

Abstract

Hepatic tissue engineering using primary hepatocytes has been considered a valuable new therapeutic modality for several classes of liver diseases. Recent progress in the development of clinically feasible liver tissue engineering approaches, however, has been hampered mainly by insufficient cell-to-cell contact of the engrafted hepatocytes. We developed a method to engineer a uniformly continuous sheet of hepatic tissue using isolated primary hepatocytes cultured on temperature-responsive surfaces. Sheets of hepatic tissue transplanted into the subcutaneous space resulted in efficient engraftment to the surrounding cells, with the formation of two-dimensional hepatic tissues that stably persisted for longer than 200 d. The engineered hepatic tissues also showed several characteristics of liver-specific functionality. Additionally, when the hepatic tissue sheets were layered in vivo, three-dimensional miniature liver systems having persistent survivability could be also engineered. This technology for liver tissue engineering is simple, minimally invasive and free of potentially immunogenic biodegradable scaffolds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques / methods
  • Cells, Cultured
  • Graft Survival
  • Hepatocytes / cytology*
  • Liver / metabolism*
  • Mice
  • Mice, Transgenic
  • Tissue Engineering / methods*
  • Tissue Transplantation