Liver cells made in the lab using skin cells: Study

By Dr. Ananya Mandal, MDMay 12 2011

In a medical breakthrough, researchers have been able to convert skin cells into liver cells. This could one day eliminate the need for organ transplants, they say.

The study at the Shanghai Institute for Biological Sciences was conducted on mice wherein they successfully generated the main type of liver cell - called a hepatocyte - from a skin cell. According to the study, published this week in Nature, “when transplanted into mouse models of liver injury, the hepatocyte-like cells can repopulate the livers and restore their function.” The paper is titled “Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors.”

The authors tested the cells as transplants in mouse models of liver injury. While all untreated animals showed weight loss and died within seven weeks, five of twelve animals transplanted with the induced hepatocytes were still alive after eight weeks and showed increased body weight. In contrast with the control mice, the treated animals’ livers looked normal, and the transplanted hepatocytes had replicated and comprised 5% to 80% of the liver hepatocytes in the surviving animals.

According to Australian liver expert Professor Geoff McCaughen, while stem cells have been seen to make the transition, this was the first time the “reprogramming” technique worked with skin cells. “They're not perfectly functional like a normal liver cell, but they're probably 50 per cent or more there,” said Professor McCaughen, head of the liver transplant unit at Sydney's Royal Prince Alfred Hospital. “The genes which are used in programming and making it [a] liver cell … those genes have been put in to a skin cell and made functional,” he explained.

The liver is an important organ that manufactures and digests proteins, produces blood-clotting factors, metabolizes glucose, gets rid of toxins and maintains blood sugar and energy levels. “You can't live without these crucial liver cells, called hepatocytes, without them you die - this is liver failure,” he said. About 200 people are on the waiting list for liver transplants in Australia, and 10 per cent of them would die while in line, Professor McCaughen said.

The authors conclude that their achievement supports the general principal that cell lineages can be converted by regulating the transcriptional network. “To our knowledge, this is the first time that adult fibroblasts have been directly converted to functional induced hepatocyte cells,” they add. “Thus, induced hepatocyte cells represent an alternative source of hepatocytes for disease modeling, transplantation, and tissue engineering. To apply this approach for the purpose of regenerative medicine, future studies will need to address whether human fibroblasts and other cell types could be successfully converted to functional induced hepatocyte cells.”