Liver Cells Grown from Human Skin Cells

The study was led by Stephen A. Duncan, D. Phil., a professor of human and molecular genetics, and professor of cell biology, neurobiology, and anatomy, from the Medical College of Wisconsin (Milwaukee, WI, USA). "This is a crucial step forward towards developing therapies that can potentially replace the need for scarce liver transplants, currently the only treatment for most advanced liver disease,” said Dr. Duncan.

Liver disease is the fourth leading cause of death among middle-aged adults in the United States. Loss of liver function can be caused by several factors, including genetic mutations, infections with hepatitis viruses, by excessive alcohol consumption, or chronic use of some prescription drugs. When liver function goes awry it can result in a wide variety of disorders including diabetes and atherosclerosis and in many cases is fatal.

The Medical College research team generated patient-specific liver cells by first repeating the work of Dr. James Thomson and colleagues at University of Wisconsin-Madison who revealed that skin cells can be reprogrammed to become cells that resemble embryonic stem cells. They then tricked the skin-derived pluripotent stem cells into forming liver cells by mimicking the normal processes through which liver cells are made during embryonic development. Pluripotent stem cells have the capacity to develop into any one of more than 200 cell types in the human body.

At the end of this process, the researchers found that they were able to very easily produce large numbers of relatively pure liver cells in laboratory culture dishes. "We were excited to discover that the liver cells produced from human skin cells were able to perform many of the activities associated with healthy adult liver function and that the cells could be injected into mouse livers where they integrated and were capable of making human liver proteins,” commented Dr. Duncan.

Several studies have shown that liver cells generated from embryonic stem cells could potentially be used for therapy. However, the possible use of such cells is limited by ethical considerations associated with the generation of embryonic stem cells from preimplantation embryos and because embryonic stem cells do not have the same genetic make-up as the patient.

Although the investigations are still at an early stage, the researchers believe that the reprogrammed skin cells could be used to study and potentially treat metabolic liver disease. The liver may be especially suitable for stem cell-based therapies because it has a remarkable capacity to regenerate. The liver is a central regulator of the body's metabolism and is responsible for controlling sugar and cholesterol levels, secretion of a variety of hormones, production of blood clotting factors, and has a fundamental role in preventing toxins from damaging other organs in the body.

It is possible that in the future a small piece of skin from a patient with loss of liver function could be used to produce healthy liver cells, replacing the diseased liver with normal tissue.

The Medial College researchers are currently producing reprogrammed cells from patients suffering from diabetes, hyperlipidemia, and hypercholesterolemia in an effort to identify new treatments for these diseases. 

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