In Vivo Visualization and Portally Repeated Transplantation of Bone Marrow Cells in Rats with Liver Damage

Abstract

Recent reports have raised concerns over the feasibility of differentiating bone marrow cells (BMCs) into functional hepatocytes. Such augmentation is considered necessary for potential clinical use of these cells in liver diseases. The present investigation was designed to determine the kinetics of transplanted BMCs and evaluate the effects of repeated bone marrow transplantation (BMT) in rat models of CCl(4)-induced liver damage. The early kinetics of transplanted BMCs was evaluated with a charge-coupled-device (CCD) camera using BMCs obtained from green fluorescent protein (GFP) transgenic (Tg) rats and followed up with in vivo imaging system (IVIS) using BMCs obtained from firefly luciferase (luc) Tg rats. We used a portal infusion system for repeated BMT. BMCs were transplanted via a peripheral vein or the portal vein (PV) once or repeatedly using this system. The results revealed that BMCs accumulated more in the damaged liver than in the intact liver. In the experimental group receiving repeated BMT via the PV, the liver fibrosis was milder than that in the group not receiving BMT, and large clusters of albumin-producing cells were detected by albumin staining. The injected BMCs were shown to accumulate in the damaged liver. This strategy of repeated BMT has potential clinical use in enhancing the number of albumin-producing cells and suppressing liver fibrosis. This combination of beneficial effects may contribute to the benefits of cell transplantation therapy. Demonstration of the benefits of BMT in this study may be expected to have great significance for clinical trials.