Damaged liver ‘could be repaired using adult stem cells’

For the first time, researchers have found a way to repair damaged livers using adult stem cells.

The finding by Johns Hopkins researchers could one day be used as an alternative to liver transplant in patients with serious liver diseases, bypassing long waiting lists for organs and concerns about immune system rejection of the donated tissue.

They have demonstrated that human liver cells taken from adult stem cells – known as induced-pluripotent stem cells (iPSC) – coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage.

“Our findings provide a foundation for producing functional liver cells for patients who suffer liver diseases and are in need of transplantation,” said Yoon-Young Jang, assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.

“iPSC-derived liver cells not only can be generated in large amounts, but also can be tailored to each patient, preventing immune-rejection problems associated with liver transplants from unmatched donors or embryonic stem cells,” she added.

iPSCs are made from adult cells that have been genetically reprogrammed to revert to an embryonic stem cell-like state, with the ability to transform into different cell types.

Human iPSCs can be generated from various tissues, including skin, blood and liver cells.

Although the liver can regenerate in the body, end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy the liver”s regenerative ability, said Jang.

Currently, the only option for those patients is to receive a liver organ or liver cell transplant, a supply problem given the severe shortage of donor liver tissue for transplantation.

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In addition, mature liver cells and adult liver stem cells are difficult to isolate or grow in the laboratory, said Jang.

By contrast, iPSCs can be made from a tiny amount of many kinds of tissue; and the embryonic stem-like iPSCs can grow in laboratory cultures indefinitely.

For the study, Jang and colleagues generated human iPSCs from a variety of adult human cells, including liver cells, fibroblasts (connective tissue cells), bone marrow stem cells and skin cells.

They found that though the iPSCs overall were molecularly similar to each other and to embryonic stem cells, they retained a distinct molecular ‘signature’ inherited from the cell of origin.

Next, they chemically induced the iPSCs to differentiate first into immature and then more mature liver cell types. Regardless of their origin, the different iPSC lines all showed the same ability to develop into liver cells.

Using mice with humanlike liver cirrhosis, the researchers then injected the animals with either 2 million human iPSC-derived liver cells or with normal human liver cells.

They discovered that the iPSC-derived liver cells engrafted to the mouse liver with an efficiency of eight to 15 percent, a rate similar to the engraftment rate for adult human liver cells at 11 percent.

The study is published in the May 11 issue of the journal Science Translational Medicine.

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