ISOLATED HEPATOCYTES - PAST, PRESENT AND FUTURE

The first technique for large-scale preparation of isolated hepatocyte s was described in 1953 and involved perfusion of rat liver under pres sure with a Ca2+-free solution containing a chelating agent. Various m odifications of this technique were in use over the next ten years, un til it was demonstrated that cells prepared in this manner were grossl y damaged, losing most of their cytoplasmic enzymes during the prepara tive procedure. The successful preparation of intact isolated hepatocy tes by collagenase-treatment of liver was achieved in 1967, and the wi despread use of intact hepatocyte suspensions was accelerated by the d evelopment soon after of high-yield preparative techniques involving p erfusion of the liver with a medium containing collagenase. The introd uction of the isolated hepatocyte preparation has enabled experimental studies that otherwise would not be feasible. Important advances have been the use of cultured hepatocytes, frequently of human origin, for the investigation of the metabolism and toxicology of potential thera peutic agents. Success in this field has been achieved through the ste ady improvement in techniques for the maintenance in culture of differ entiated hepatocytes, and in particular their cytochrome P450 complexe s. Another area showing considerable promise is the employment of hepa tocytes, generally from a porcine source, in temporary support systems for patients with acute liver failure. Our own studies have concentra ted on the demonstration of long-range interactions between hepatocyte compartments which suggest that energy transfer between cell compartm ents can take place without ATP turnover.