Role of bone marrow derived progenitor cells in liver regeneration:

When part of the liver is removed at surgery or in other (medical) forms of injury to the liver, the liver regenerates. Bone marrow derived progenitor cells maybe involved in hepatic regeneration, however, there is no consensus as to which progenitor cell is involved in this process.

We studied CD 34+ve cells in peripheral blood (bone marrow derived progenitor cells) in 6 patients with acute on chronic liver failure and peripheral blood leukocytosis (white blood cell counts: 24515 (18100 – 51000), median (range).  These patients did not have sepsis or any other explanation for the leukocytosis. The peripheral blood fraction of CD 34 +ve cells in the study patients was 0.058 (0.011 – 0.078), median (range). (CD 34 +ve cells < 0.4 % in peripheral blood is regarded as normal).

This preliminary study did not find an increase in CD 34+ve cells in the peripheral blood in the patients studied. Increase in peripheral blood CD34+ cells in patients with acute liver injuries but not in chronic liver disease has been reported. Another recent report showed recruitment of hematopoietic progenitor cells with a CD133(+)/ CD45(+)/ CD14(+) phenotype in 61% of cirrhotic patients. We plan further studies using different markers of progenitor cells in different phases of injury and healing in the liver.

To establish an animal model of liver injury (prior to stem cell therapy):

We have focused specifically on 2 types of liver diseases which result in liver failure, which are important clinical problems.
Acute fatty liver of pregnancy is a cause of significant maternal morbidity and (earlier) of mortality at our centre.  Hepatic microvesicular steatosis is the pathological hallmark of acute fatty liver of pregnancy. To understand the disease process better, we have previously studied hepatic microvesicular steatosis induced by intraperitoneal administration of valproic acid in a rat model.

As mice based stem cell reagents are more readily available, we decided to create a mouse model of hepatic microvesicular steatosis.  Intraperitoneal valproate was administered into Swiss Albino and C57BL/6J mice strains. Though our experiment resulted in some degree of microvesicular steatosis, it was inadequate to induce acute liver failure while maintaining an intermediate level of mortality.
We plan to study another mouse model of liver injury, which has been presented to the animal ethics committee and is awaiting approval.

Once the mouse model of liver injury is established, we will proceed to see if stem cell therapy will help in recovery from the illness.