Is there an optimal concentration of contransplanted islets of langerhans for stimulation of hepatocytes in three dimensional matrices

Background Hepatocyte transplantation using three dimensional matrices is u nder investigation as an alternative therapy for several liver diseases. Fo r sufficient transplantation results hepatotrophic stimulation is necessary . We investigated the stimulatory effect of cotransplanted pancreatic islet s in different ratios. Methods. Lewis rats were used as donors and recipients. A portocaval shunt (group A) or sham operation (groups B-G) was performed 1 week before hepato cyte transplantation. Four polyvinyl-alcohol matrices each containing 1.25 x 10(7) hepatocytes (groups A and B) or 1.25 x 107 hepatocytes and 125 (C), 250 (D), 500 (E), or 750 (F) islets were implanted between small bowel mes enteric leaves. In group G, medium soaked matrices mere implanted. One mont h after implantation, specimens were harvested and investigated using album in-RNA in situ hybridization, and insulin, glucagon, and bromodesoxy uridin e immunohistochemistry. The hepatocyte area was assessed using image analys is. Results. Hepatocyte area and proliferation ratio increased depending on the number of cotransplanted islets with a peak at 40 islets per 1 million hep atocytes (group E). Cotransplantation of islets in higher concentrations di d not further increase hepatocyte area or proliferation ratio. Hepatocytes in all groups expressed albumin RNA at normal transcription levels as compa red to standard liver sections. Islets displayed insulin and glucagon in ph ysiological distribution. Discussion. Three-dimensional matrices provide a sufficient environment for transplanted hepatocytes and islets. The hepatotrophic effect of cotranspl anted islets is comparable to portocaval shunting and has a saturation limi t at 40 islets per 1 million hepatocytes. For further application of islet cotransplantation, this ratio seems to be preferable.