Clinical Research of Autologous Transplantation of Bone Marrow Stem Cells on Decompensate Cirrhosis Patients
|School||Dalian Medical University|
|Keywords||bone marrow stem cells transplantation liver cirrhosis ALB PTA|
Objective: Decompensate cirrhosis has no effective therapy to date. The effectiveness of treatment is limited for the cause and it is difficult to prevent the further development of liver cirrhosis. The key step of its treatment is to control the pathogenic factors of liver cirrhosis in the early stage. For end-stage decompensate cirrhosis, liver transplantation is the only effective treatment. However, due to a severe shortage of organ donors, much interest has focused on the contribution of bone marrow stem cells to liver regeneration. The aim of the present study is to provide autologous bone marrow derived stem cells (BMSCs) as a potential therapeutic for patients with end-stage cirrhosis and to further discuss the safety, feasibility and therapeutic effect of the regimen.Method: Twenty four patients with decompensate cirrhosis were enrolled and underwent autologous BMSCs transplantation. 150~230 ml of bone marrow blood were collected from each patient. Then heparinized bone marrow blood (125 ml/unit) was isolated with density gradient centrifugation. The isolated BMSCs were injected into the liver through liver artery by means of the intervention route. Different index were observed at different time points between pre-operation and post-operation, such as ALB, TBil, clinical symptoms score, adverse effects, complications and prognosis.Results:1. No adverse effects occurred after the transplantation.2. The score of clinical symptom: the score of 2w, 4w, 8w, 12w and 24w after transplantation improved significantly compared to that of the pre-transplantation (P<0.01). The average score of clinical symptom before transplantation was 2.13±0.68;The average score at 12w after transplantation was 1.05±0.69, which indicated the most significant amelioration. The average score at 24w (1.25±0.85) was less compared to 12w but still more than that in the pre-operation.3. The change of ALB: Among ChildA-B patients, the serum ALB level began to increase 2w after transplantation. While the level at 12w reached the peak concentration. 24W after treatment, serum ALB decreased, but still higher than the level before treatment. There were significant differences in ALB between2w, 4w, 8w, 12w, 24w after and before BMSCs infusion (P<0.01)。However it was still noticeable that the ALB level in Child C patients took on a descending tendency in the duration of 24 weeks. 2w,4w,8w,12w and 24w after treatment compared with before treatment in serum ALB was no significant difference(P>0.05).4. The change of PTA: Among ChildA-B patients, the serum PTA level began to increase 2w after transplantation. While the level at 8w reached the peak concentration. 24W after treatment, PTA decreased, but still higher than the level before treatment. 2w,4w, 8w, and 12w PTA compared to preoperative level have significant difference(P<0.01). The PTA at 24w had no statistical difference compared to preoperative level (P>0.05). The PTA in ChildC patients compared with before treatment was no significant difference(P>0.05).5. The change of TBil: ChildA-B patients at 2w,4w, 8w, 12w and 24w compared to preoperative level in TBil have no significant difference after BMSCs infusion(P>0.05). It was also observed that there was no statistical difference in ChildC patients (P>0.05).6. The complications in half year after BMSCs transplantation: 3 in 24 patients (12.5%) had upper gastrointestinal bleeding (UGIB), 4 (16.6%) had hepatic encephalopathy (HE), 3 (12.5%) had infection, 1 (4.1%) had primary hepatic carcinoma (HCC).7. Death circumstances in half year after BMSCs transplantation: 4 patients (16.6%) died from complications or hepatic cirrhosis complications, other than hepatic failure. One died from pneumonia associated septic shock, 3 months after transplantation. One died from hepatic encephalopathy induced by incomplete bowel obstruction and secondary peritonitis, 4 months after transplantation. Two died from UGIB, 3 and 6 months after transplantation respectively, one of which combined with hepatic encephalopathy induced by UGIB.Conclusions:1. Liver artery infusion of BMSCs is effective on treatment of hepatic cirrhosis.2.Liver function ChildC grade, without obvious therapeutic effect.3. Although there was clinical and biochemical improvement in a large percentage of patients who received the transplantation, a few patients have poor prognosis due to severe complications such as UGIB, infection and HE.