Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation

Abstract

Purpose of ReviewWe will review the recent developments of cell sheet technology as a feasible tissue engineering approach. Specifically, we will focus on the technological advancement for engineering functional liver tissue using cell sheet technology, and the associated therapeutic effect of cell sheets for liver diseases, highlighting hemophilia.Recent FindingsCell-based therapies using hepatocytes have recently been explored as a new therapeutic modality for patients with many forms of liver disease. We have developed a cell sheet technology, which allows cells to be harvested in a monolithic layer format. We have succeeded in fabricating functional liver tissues in mice by stacking the cell sheets composed of primary hepatocytes. As a curative measure for hemophilia, we have also succeeded in treating hemophilia mice by transplanting of cells sheets composed of genetically modified autologous cells.SummaryTissue engineering using cell sheet technology provides the opportunity to create new therapeutic options for patients with various types of liver diseases.

Cell sheet tissue engineering: Cell sheet preparation, harvesting/manipulation, and transplantation

“…HB‐EGF‐bound heparin‐immobilized temperature‐responsive surfaces facilitate the fabrication of hepatocyte sheets with preserved hepatic functions . Tissue engineering of the liver is an attractive approach for the treatment of liver diseases such as enzyme deficiencies and hemophilia . Engrafted hepatocyte sheets in a pre‐vascularized subcutaneous site exhibited long‐term secretion of liver‐specific enzymes .…”

“…48 Tissue engineering of the liver is an attractive approach for the treatment of liver diseases such as enzyme deficiencies and hemophilia. 54 Engrafted hepatocyte sheets in a pre-vascularized subcutaneous site exhibited long-term secretion of liver-specific enzymes. 55 However, isolated hepatocytes from the liver gradually lose their phenotypic functions during the cultivation of a hepatocyte monolayer on a PIPAAm surface.…”

Unveiling Mesenchymal Stromal Cells’ Organizing Function in Regeneration

“…In our studies CS have performed better than suspended MSC for treatment of ischemia, nerve repair [57,58,61], deep wound healing [62] and pressure ulcer (data unpublished). Recent papers describing use of CS for liver regeneration [63] or bone healing [64] often omit direct "head to head" comparison of outcomes after CS or suspended delivery yet most of them report long-term survival of transplanted cells suggesting that it mediates therapeutic outcome.…”

Engineered mesenchymal stem-cell-sheets patches prevents postoperative pancreatic leakage in a rat model

“…Technologies that use cells to induce wound healing or tissue regeneration are rapidly progressing 8 – 10 , especially with the use of mesenchymal stem cells (MSC) that have functions in both regeneration and immune response. Recently, several clinical applications of MSC have been reported.…”