Hello, everyone. My name is Oh, Jae-Hoon, a PhD student of Department of Bio and Brain
Engineering. Today topic is that immune cell therapy for liver disease. Before a professor’s
lecture, I will introduce some basic information of liver and liver disease.
Liver is the largest organ of the body. Liver is a reddish brown organ with four lobes of
unequal size and shape. It is located in the right side of the abdominal cavity under the
diaphragm. Liver plays an important role in synthesis of proteins such as albumin, clotting
factors and complements.
Liver is involved in detoxification and storage. In addition, it participates in the metabolism
of lipids and carbohydrates. The liver is the only human organ regenerating
lost tissue. 25% of a liver can regenerate into a whole liver.
The liver gets dual blood supply from the hepatic arteries and hepatic portal vein.
The liver is composed of hepatocyte, kuppfer cell, sinusoidal endothelial cell, hepatic
stellate cell, and so on. 80% of the liver volume is occupied by hepatocytes.
Hepatocytes play a vital role of hepatic function. Sinusoidal endothelial cells make sinusoidal
blood vessel which serve as a way for the oxygen-rich blood from the hepatic artery
and the nutrient-rich blood from the portal vein. Kupffer cells are located in the wall
of sinusoids. They act as macrophages. Hepatic stellate cells are found in the space between
the sinusoids and hepatocytes. In normal liver, the function and role of hepatic stellate
cells is unclear. Recent evidence suggests a role as an antigen-presenting cell.
When the liver is damaged, stellate cells can secrets extracellular matrix (collagen).
There are many kinds of liver disease. The most widely spread liver diseases are fatty
liver, hepatitis, cirrhosis and liver cancer. Fatty liver is a condition that fat accumulate
in liver cells. Microscope shows the large vacuoles of fat in liver tissue.
Hepatitis is an inflammatory disease of the liver. Inflammation is caused by viruses,
alcohol, toxin and so on. Cirrhosis is chronic liver disease characterized by replacement
of healthy liver tissue by fibrosis, scar tissue. Liver cancers are malignant tumors
that grow on the surface or inside the liver. The most frequent liver cancer is hepatocellular
carcinoma. It accounts for 75% of all liver cancers, Another type of cancer formed by
liver cells is hepatoblastoma, which is formed by immature liver cells. It is a rare malignant
tumor that develops in children.
I’ll explain cirrhosis in more details. Cirrhosis is mostly caused by alcoholism,
hepatitis virus, autoimmune, drug, and fatty liver which induce liver injury. In response
to liver injury, extracellular matrix or scar is accumulated. This process is called fibrosis.
Accumulation of extracellular matrix is considered as wound healing process.
However If liver is damaged by long-term injury, scar tissue by fibrosis replaces healthy tissue.
Over time this process results in cirrhosis of the liver. Scar tissue of cirrhosis is
not able to do normal hepatic function. Once cirrhosis has developed, the serious complications
of liver disease may occur, including liver failure and liver cancer.
What is the cellular mechanism of fibrosis? Liver injury activates hepatic stellate cells
and Kuppfer cells. Stellate cell activation is a key pathogenic feature underlying liver
fibrosis and cirrhosis. Activated hepatic stellate cells produce a huge amount of extracellular
matrix (collagen fibers) and many cytokine mediators (transforming growth factor-beta,
interleukin-6 and monocyte chemoattractant protein-1). Interaction of hepatic stellate
cells and immune cells in liver is related in the progression of liver fibrosis.
Some immune cells ameliorate liver fibrosis.
What is the treatment for cirrhosis? Currently, cirrhosis can't be cured.
However, it is possible to manage the symptoms and any complications, and slow its progression.
Because cirrhosis is irreversible, treatment aims to stop the disease from getting worse.
The treatment depends on the cause of cirrhosis. If cirrhosis is caused by viral hepatitis,
patients may be treated with anti-viral drugs. If the patients are heavy drinkers, they are
advised to stop drinking alcohol. If the patients are overweighed, they are advised to lose
weight. If cirrhosis is very severe and the liver stops working, the only treatment option
is liver transplantation.
There are many scientific efforts to develop new treatment methods for cirrhosis. Professor
Jeong Won il (KAIST) and Kim Ja Kyoung (Yonsei University college of medicine ) have developed
new and novel treatment for liver cirrhosis. They used immune cell therapy.
Autologous bone marrow cells were transplanted into the patients of cirrhosis. Autologous
bone marrow cells increase the production of cytokines which inhibited the hepatic stellate
cells from secreting collagens. In this clinical trial, the immune cell therapy was effective
to improve 70% of the cirrhosis patients.
Today speaker is Professor Jeong won ill, at KAIST Graduate School of Medical Science
and Engineering. Prof. Jeong will give us a lecture on immune cell therapy for liver
disease. Thank you for listening.