Clinical Observation Of Umbilical Cord Mesenchymal Stem Cells To Treat End-Stage Liver Cirrhosis Patients

Hepatic cirrhosis are caused by a variety of liver damage, liver cells showing degeneration and necrosis, fibrosis, nodular regeneration, lobular architecture distortion, blood circulation route to be converted, eventually leading to cirrhosis. Based on etiology, hepatic cirrhosis are classified to viral cirrhosis, alcoholic cirrhosis, parasitic liver cirrhosis, toxic cirrhosis, biliary cirrhosis, autoimmune cirrhosis, congestive cirrhosis, cryptogenic cirrhosis and so on. Hepatic cirrhosis caused by Hepatitis B virus is very common in China. According to statistics, about 9,300 million people carry hepatitis B virus, of which about 30 million are hepatitis B patients. Due to lack of effective treatment for hepatitis B virus and high cost of treatment, many patients can not receive long-term treatment ultimately, and eventually lead to cirrhosis. Patients of hepatic cirrhosis often suffer from portal hypertension and liver dysfunction, and finally result in death due to hepatic encephalopathy and gastrointestinal bleeding. Therefore, the treatment of hepatic cirrhosis is a difficult task. Effective therapy for hepatic cirrhosis is liver transplantation. But it is hard to be carried out in clinical work for lack of liver donor. More and more scientists focus on some other methods replacing liver transplantation. Mesenchymal stem cells is one of the options for treatment of hepatic cirrohsis.Mesenchymal stem cell is a member of stem cells. Mesenchymal stem cells are mainly in the bone marrow, umbilical cord, cord blood, embryos. Mesenchymal stem cells received much attention because of multiple differentiation potential, hematopoietic support, immune regulation, self-replication and other characteristics. Mesenchymal stem cells can serve as ideal seed cells for inflammation caused by disease and organ repair due to aging. In vivo or in vitro conditions, MSCs can be induced and differentiated into bone, cartilage, fat, muscle, tendon, nerve, liver cells, heart and so on. MSCs'continuous passage has multiple differentiation potential. Mesenchymal stem cells are very early to be used clinically. Bone marrow extraction is invasive and increase patients,suffering. A growing number of scholars have been working on the umbilical cord derived mesenchymal stem cells. Umbilical cords are easy to be collected non-invasively, and therefore umbilical mesenchymal stem cells are commonly used in treatment of a variety of diseases in clinical practice, including liver cirrhosis.Objective: Cultivate mesenchyma stem cells the full-term childbirth embryo umbilical cord,explore the method of umbilical cord mesenchymal stem cells separation in vitro, proliferation, identification, and observe the efficacy in treating of end-stage hepatic cirrhosis.Methods: Collect newborn umbilical cord under sterile conditions, culture mesenchymal stem cells after separation, take cells for flow cytometry checking CD29, CD105, CD34, CD45. Select 50 cases of liver cirrhosis, 26 patients received basic medication and MSCs transplantation as well by way of forearm vein or the hepatic artery. Liver function, blood coagulation function, clinical symptoms, signs, symptoms and adverse reactions were monitored postoperatively. In addition, 24 patients with cirrhosis are randomly selected to receive regular medical treatment as control.Results:(1) Mesenchymal stem cells from umbilical cord are spiral-shaped growth in culture. Cells of passage 1 were digested and passaged. Its adherence time is about 48h. It covered about 80% after 2-3w. Passage 3 - passage 6 cells grow faster, adhere in 24h covering 70% in 48h, covering 80% in 72h. There is no significant difference in proliferation and differentiation within the passage 6.(2) The phenotype of cells were CD29, which is mesenchymal stem cells' specific marker, but did not express hematopoietic stem cell surface markers CD34, CD45. The cultured mesenchymal stem cells cells and bone marrow mesenchymal stem cells are in the same of phenotypic expression.(3) After UCMSCs treatment, the level of albumin, prealbumin and fibrinogen were significantly increased in treatment group than in control group (P<0.05), and the levels of prothrombin time was obviously reduced (P<0.05).(4) One week after treatment, the symptoms such as fatigue, abdominal distension, anorexia have been improved in treatment group. 12 weeks later, the amounts of ascites were significantly reduced. No serious adverse reactions and complications occurred in 26 cases of transplant patients after treatment.Conclusion:(1) Mesenchymal stem cells from isolated umbilical cord are less damaged after cryopreservation and recovery. After several passages, cells had less differentiation, more stable proliferation. (2) Human umbilical cord mesenchymal stem cells were detected by flow cytometry, the expression of mesenchymal stem cell phenotype, did not express hematopoietic stem cell phenotype. Cultured Cells and bone marrow mesenchymal stem cells were in the same of phenotypic expression.(3) Treatment of hepatic cirrhosis by human umbilical cord mesenchymal stem cells can increase patient's ALB, PA, Fbg, shorten the PT and improve clinical symptoms.(4) Human umbilical cord mesenchymal stem cell transplantation in patients with hepatic cirrhosis is safe.