[Autologous bone marrow cell infusion therapy for liver cirrhosis--now and future]

Infused (transplanted) green fluorescent protein (GFP)-positive bone marrow cells (BMCs) migrated into the peri-portal regions of the cirrhotic mouse liver induced continuous CCl4 injection without irradiation (without bone marrow ablation). The infused GFP-positive BMCs differentiated into hepatoblasts detected with Liv2-antibody and then differentiated into albumin-producing hepatocytes. The differentiation "niche" induced by persistent liver damage due to continuous CCl4 injection seems to be an essential factor. Microarry analysis showed that at an early stage after BMC infusion through mouse tail vein, the genes related to degradation of extracellular matrix (ECM) e.g. MMP-9 were activated. BMC infusion improved liver fibrosis and the survival rate. Recent our finding indicates that mesencymal bone marrow cells will differentiate to hepatocytes and FGF2 will accelerate this differentiation of BMC to hepatocyte. Based on the results obtained in basic research using the GFP/CCl4 model, human trials are now undergoing. We have done this autologous bone marrow cell infusion therapy for 19 patients with advanced liver cirrhosis. The clinical study of liver cirrhosis (LC) cases that underwent autologous bone marrow cell infusion from peripheral vein is as follows. Subjects were LC patients with T.B. of < 3.0 mg/dl, Plt of > 5(10(10)/l) and no viable hepatocellular carcinoma by diagnostic imaging. Autologous bone marrow cells (BMCs, 400 ml) were isolated from the ilium under general anesthesia. BMCs were separated by cell washing and were infused via the peripheral vein. After BMC infusion, liver function was monitored by blood examination for 24 weeks. We could follow 9 cases more than 6 months so far. After washing, 5.20 +/- 0.63 x 10(9) BMCs were infused into LC patients. Serum albumin level and total protein were significantly improved at 24 weeks after BMC infusion (p < 0.05). The Child-Pugh score was significantly improved at 4 week and 24 weeks after BMC infusion (p < 0.05). No major adverse effects were noted. In conclusion, autologous BMC infusion might be considered as a novel treatment for advanced LC patients.