Historical perspectives of hybrid hepatic assist devices: tissue sourcing, immunoisolation, and clinical trial.

Abstract

A hybrid hepatic assist device using canine liver tissues was developed and clinically applied 38 years ago. However, for many years practical hybrid hepatic assist devices were not clinically introduced owing to the many difficulties encountered in employing cultured hepatocytes. These problems include: (1) maintenance of viable cultured cells, (2) maintenance of normal hepatocyte function with these cells, (3) elimination of toxic substances generated by non-viable cultured and/or stored cells, (4) elimination of immunological factors generated by cultured cells and by the patient, and (5) difficulties of the biocompatible immunological barrier for cells against the patient. Fortunately, recent progress in apheresis and biomaterial technologies enable us to isolate cultured cells immunologically and yet maintain effective metabolic functions for the patient. These technologies generate an immunological barrier of a hybrid hepatic assist device for the patients. Proper adsorption columns developed for apheresis procedures enable us to remove the toxic substances released by non-viable cells. Recent development of oxygen-carrying macromolecules enable us to provide sufficient oxygen supply to the cultured cells and to maintain their normal cellular function, not only during the cultured period of time, but also during their actual clinical application. Together with the advancement of cell culture technologies, including the proper cultured environments and cellular seeding environments, these technologies, primarily developed for therapeutic apheresis, should be able to provide more effective and safe hybrid artificial organs.