Liver Cells Generated from Skin Cells

Hepatology, Nov 15, 2009 Si-Tayeb K, et al.

Liver failure is a major cause of death world-wide, precipitated primarily by Hepatitis infection and alcohol use. Stem cell therapy of liver failure has been performed previously by extracting stem cells from the bone marrow, purifying the active portion of the stem cells, and subsequently administering the stem cells either intravenously, or into the blood vessel feeding the liver. The objective of bone marrow stem cell therapy is to stimulate multiplication of the existing liver stem cells, as well as to reduce the fibrosis, or scar tissue, that exists. There have been positive reports of patient improvement following this procedure, some of which are described in the following video Stem Cell Therapy for Liver Failure

A recent study from the Department of Cell Biology at the Medical College of Wisconsin suggests that there may be another way to use stem cells for liver failure. The researchers, led by Dr. Si-Tayeb, reported today that it is possible to generate liver cells, called hepatocytes, from stem cells that are derived from skin. These types of stem cells, inducible pluripotent stem cells (iPS) are generated by inserting genes into skin cells that are normally found in embryonic stem cells and/or cancer. Once these genes are activated, the skin cell changes shape over the period of weeks, takes the appearance of an embryonic stem cell, and can become any cell in the human body when exposed to the right conditions.

By growing the iPS cells in tissue culture conditions that resemble a developing liver, the researchers have generated large numbers of mouse and human liver cells. These cells possess the same metabolic enzymes as normal liver cells, and produce comparable levels of important liver-secreted proteins such as albumin. In order to test if the cells actually can function as liver cells in a biological system, the generated cells were administered to mice whose livers have been damaged by exposure to the toxin carbon tetrachloride. Mice that received the artificially generated liver cells, but not control mice, had a recovery in production of liver enzymes.

The ability to generate large numbers of liver cells is important not only from a therapeutic point of view, but also for screening of drugs. Currently pharmaceutical companies use animals for experiments in order to understand whether their drugs will have toxic effects on organ systems such as the liver. By being able to produce large amounts of human liver cells in vitro, it will be possible to test drugs that are meant to be used by humans, in human cells. This is anticipated to reduce the drug development cycle time, and hopefully accelerate the creation of new medicines.