Abstract
P683 Aims: Bone marrow cell (BMC) has been intensively investigated whether these cells could be used for the treatment of liver dysfunctions. However the effectivities of BMC transplantations is still not clear because survival period of transplanted cells were not long enough to support recipient liver functions. We have developed a novel technique which allows repeated infusion of BMC into the portal system via an indwelling catheter. In this study we have developed an effective intraportal transplantation protocol to extend survival time of transplanted cells. Methods: 6weeks old male Nagase Analbuminemic rats (NAR) were injected subcutaneously every 3.5 days with CCl4 dissolved in equal volume of olive oil at a dose of 2.0 ml/kg body weight for 8weeks. Repeated intraportal infusion of 5 x 10(6) rat BMC isolated from 6weeks old female enhanced green fluorescent protein transgenic (EGFP-tg)rat twice a week for the last 4weeks via an indwelling catheter connected to a subcutaneous port. Another NAR underwent repeated intraportal infusion of Dulbecco’s Modified Eagle’s Medium (DMEM). For assessment of liver function, Body and liver weight was measured and blood was obtained for total bilirubin, albumin, PT, transaminase and ammonia. We also evaluated the improvement of fibrosis by histology and repopulating cells by immunohistochemistry. Results: At 4 weeks after the start of BMC transplantation (BMT), we found no significant difference in their total body weight (BMT model: 170g, Control model: 166g). But their liver weight of BMT groups remarkably increased (BMT model: 14.7g, Control model: 11.2g). We also observed macroscopically different between them. Control group liver was white and atrophic, but the liver from BMT model was red and expanded. Microscopic studies revealed that the liver of rat receiving continuous BMT showed decreases in fibrosis, necrosis and inflammatory infiltration. And in the BMT rat, GFP positive cells were found around the portal vein. Prothrombin time(PT), total bilirubin, serum ammonia and transaminase were also significantly better in BMT model compared with control model. Conclusions: Repeated bone marrow cell transplantation via a portal catheter can decrease liver fibrosis and improve liver function of rats with liver cirrhosis and may be useful in the treatment of cirrhosis in humans.
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