Functional Tissue Engineering of the Liver and Islets

Abstract

Cell-based therapies by using hepatocytes and islets have recently been evaluated as a new therapeutic modality for patients with many forms of liver diseases and insulin-deficient diabetes mellitus. In most of the recently conducted clinical trials, cells have been delivered into liver vasculatures by infusing them through the portal circulation. More recently, tissue engineering-based approaches have spurred significant interests, using hepatocytes and islets in which small but functional new tissues would be created in vivo. Under circumstances in which a higher level of cell engraftment could be obtained, these approaches could provide therapeutic effects. Considerable efforts have been given to sustaining engineered tissues and maintaining their therapeutic effects. This review highlights several strategies that can achieve a higher level of cell survival for creating new functional liver and islet tissues. Anat Rec,

Preservation of heparin-binding EGF-like growth factor activity on heparin-modified poly(N-isopropylacrylamide)-grafted surfaces

“…11,12 In our laboratory, a unique method to create scaffold-free and transplantable hepatic tissues was developed using a temperature-responsive culture dish. 1,2 The temperature-responsive poly(N-isopropylacrylamide) (PIPAAm)-graed surface exhibited hydrophilic/hydrophobic alterations across the lower critical solution temperature (LCST) of 32 C, resulting in reversible cell attachment/detachment. 13,14 Primary hepatocytes adhered to and formed a monolayer on the hydrophobized PIPAAm-graed surface at 37 C. Cultured hepatocyte sheets were recovered from the hydrated surface as a single layer when the temperature was decreased to 20 C. Transplantation of hepatocyte sheets was performed at a prevascularized subcutaneous site, resulting in long-term secretion of transplanted hepatocyte-specic enzymes.…”

Antimicrobial Properties of Extracellular Matrix Scaffolds for Tissue Engineering

“…Every year, millions of patients suffer traumatisms, diseases, or infections that lead to the loss of tissues such as skin [1], bone [2], nerves [3], cartilage [4], liver [5], and blood vessels, among others [6]. An option to treat these lesions is the use of grafts that provide mechanical, biological, and chemical support for cells [4], even though a common problem with these treatments is the microbial colonization despite the use of antimicrobials; their failure is due to the ineffectiveness in controlling the infection [7][8][9].…”

Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation

“…Under these current circumstances, an innovative methodological improvement that can achieve more effective cell engraftment and longer-term therapeutic effects is required for the progress of cell-based therapy for liver diseases. Liver tissue engineering, in which the liver cells are engineered and the functional liver tissues are created in vitro and in vivo, would be a promising approach for the purpose [ 16 •]. If the engineered hepatic constructs are engrafted and can maintain their hepatic function at the transplanted sites, this would enable to support the liver function in vivo for a long time period.…”