Effectiveness of polyamidoamine dendrimers modified with tripeptide growth factor, glycyl-L-histidyl-L-lysine, for enhancement of function of hepatoma cells.

Cationic polyamidoamine dendrimers are known to be highly branched cascade polymers. Tripeptide growth factor, glycyl-L-histidyl-L-lysine (GHK), was employed as a ligand for activation or attachment of cells from a rat hepatoma cell line, H4-H-E-C3, and immobilized at the terminus of the dendrimer (GHK-dendrimer) to develop a suitable surface for use as a culture substratum in the bioartificial liver support system (BAL). The growth of cells was inhibited by increasing the number of generations of GHK-dendrimers. On the other hand, urea synthesis and lidocaine clearance of the cells adhered on fifth generation GHK-dendrimers were enhanced much more than on first generation GHK-dendrimers. GHK was shown to act as a growth inhibitor and an activator of hepatoma cells. These properties of GHK are advantageous for the utilization of hepatoma cells in BAL. Ligand-modified dendrimers are very promising for the creation of a high-performance substratum for cell culture and high performance bioartificial organs, as well as for high-performance bioartificial liver systems. GHK may have the potential to be a highly useful ligand.