Hepatic lymphocyte transplantation in hyperbilirubinemic gunn rats

Hepatic lymphomyeloid cells (HLCs) are thought to contain liver stem cells. We investigated whether HLCs generated enzyme-producing cells in vivo. HLCs from normal Wistar/Shi rats and rats in which liver ischemia was induced using a portal clamp 4 days previously were studied histopathologically and characterized using flow cytometry. Splenic lymphocytes obtained from these animals were compared as a control. The proliferative activity of HLCs and splenic cells from both groups was also tested by stimulation with concanavalin A. HLCs contained a significantly higher number of NK-T cells and OV6+ cells compared with the splenic cells. The HLCs from rats in which liver ischemia was induced tended to have greater proliferative activity than those from normal rats, while the proliferative activity of splenic lymphocytes was impaired by liver ischemia. The HLCs obtained from Wistar/Shi rats with liver ischemia were then injected into hereditary hyperbilirubinemic Gunn rats to determine whether the HLCs generated enzyme-producing cells. After injection of these stimulated HLCs, the titer of serum bilirubin in the recipient rats was markedly reduced over a long time course (6.80+/-0.93 to 4.87+/-0.22 mg/dl after 1 month and 3.52+/-1.33 mg/dl after 6 months). The results of the present study indicate that HLCs have different populations than splenic cells, and ischemia-reperfusion of the liver increased their proliferative activity. HLC transplantation successfully reduced high bilirubin levels over a long time course.