Mesenchymal Stem Cell Therapy for Liver Cirrhosis
Mesenchymal Stem Cell Therapy for Liver Cirrhosis
MSCs have been studied for the treatment of liver diseases as well as non-liver diseases.
 MSCs have been successful in treating conditions like acute steroid-resistant GVHD in
 hematopoietic stem cell transplanted patients and also have shown to improve the MELD score
 in end-stage liver disease. There were no severe side effects observed in using autologous
 MSCs as a treatment option. The outcome of the studies done so far have been positive and it
 is encouraged to study the use of MSCs as cell therapy for treating liver diseases.

 The estimated rate of cirrhosis in HBV patients in Singapore is about 1.6% per year, rate of
 hepatocellular carcinoma is about 0.8% per year overall and 3.0% per year in cirrhotic
 patients. Knowing that there are not many options currently available for Liver Cirrhosis
 patients and that they have a poor prognosis with an average life expectancy of < 12 months,
 this study uses autologous MSCs to treat Liver Cirrhosis patients in Singapore. The objective
 of the study is to demonstrate that autologous bone marrow is safe to be used in patients
 with liver cirrhosis as well as demonstrate that bone marrow MSC may improve liver function
 and prolong patient survival.
Liver cirrhosis refers to extreme scarring of the liver, resulting in suboptimal function of
 the liver. It can result from a variety of causes, ranging from hepatitis B and C infection,
 excessive alcohol consumption, autoimmune causes, fatty liver and others. Irrespective of the
 cause, once the liver becomes cirrhotic, it is a downhill course.

 Liver cirrhosis is irreversible and most patients will progressively worsen over time. Once
 liver cirrhosis has reached the stage of decompensation, that is, development of jaundice,
 ascites, variceal bleeding, hepatic encephalopathy and coagulopathy the two-year survival
 drops to about 50%.

 The definitive treatment of decompensated cirrhosis is liver transplantation. While a liver
 transplantation is potentially curative, the high costs, lack of a donor, treatment-related
 mortality and the immunosuppression complications make this option possible only for a
 limited number of patients. The vast majority do not have an effective option at all, thus
 the need to develop alternative therapies. Various types of Stem Cells had been investigated
 as a regenerative therapy for liver cirrhosis. These stem cells include bone marrow
 mesenchymal stem cells (MSC), bone marrow mononuclear cells (MNC) and peripheral CD34
 positive cells. Some early studies have shown encouraging results in patients who had
 autologous bone marrow stem cell transplantation. There was improved liver function in these
 patients with cirrhotic livers.

 The sponsor is proposing a study to look into the role of MSC therapy for patients with liver
 cirrhosis in Singapore. This will be a Phase I/II study with the main emphasis on the safety
 profile first. The trial will be conducted in compliance with the protocol, GCP and local
 regulatory requirement(s).
Inclusion Criteria:

 Subjects must meet all the inclusive criteria to participate in the study:

 1. with definite liver cirrhosis, irrespective of aetiology

 2. must have Child's B or C stage

 3. must have signed an informed consent form

 Exclusion Criteria:

 Subjects with any of the following criteria are regarded as an exclusion from the study and
 will not be permitted to participate:

 1. age ≤21 years and >70 years old

 2. with life expectancy of < 6 months

 3. cancers and bone marrow malignancies

 4. patients with an active infection or multiple infections

 5. patients with uncontrolled hypertension and diabetes

 6. immunosuppressed patients (IST must have stopped at least 4 weeks prior to trial
 enrolment)

 7. patients who are HIV positive

 8. patients who are pregnant or lactating