The non-invasive cell surface modification of hepatocytes with PEG-lipid derivatives

Hepatocyte-based therapies are promising regenerative approaches for liver diseases. In this study, we sought to develop a versatile method to modify the surface of hepatocytes by immobilizing synthetic polymers around the cells. The surface of murine primary hepatocytes was modified using poly(ethylene glycol)-phospholipids conjugate bearing FITC (FITC-PEG-lipid) in suspension. Hepatocyte function was assessed in vitro by examining cell viability, plating efficiency, protein production, metabolizing activity, hepatocyte-specific gene expressions, and cytochrome P450 induction. The engraftment of the PEG-lipid modified cells was studied following transplantation to both the liver or alternate ectopic sites. Among the types of phospholipids analyzed in our study, 1,2-dimyristoil -sn-glycerol-3-phosphatidylethanolamine (DMPE) was found to be uniformly anchored to the hepatocyte cell membrane (>99% of hepatocytes). Cell surface modification using FITC-PEG-DMPE did not result in any loss of in vitro functional parameters nor affect the engraftment potential in vivo by the modified cells. This modification was also successfully performed on dispersed hepatocytes and engineered hepatocyte sheets. In all, the ability to modify the surface of isolated hepatocytes with functional proteins, instead of FITC as shown in our proof-of-concept study, has the potential to move hepatocyte-based cell therapy another step forward as a viable therapeutic application.