Patients with advanced liver disease can be treated with stem cells taken from their own skin or blood.
Researchers have found a way to cheaply produce millions of the cells that can be injected into the organ and help regenerate it. The technique involves converting skin and blood cells back to their original stem cell state and then into liver cells.
These were then injected into a liver with cirrhosis. More than a tenth of the stem cells – – the most basic form of cell that can convert into any other cell – grafted on to the liver and started working without any significant side-effects. The advantage of using stem cells taken from skin or blood – known as induced-pluripotent stem cells (iPSC) – is that they are cheap and can be multiplied easily in the laboratory. Because they are from the patient there is also less danger of the body having a reaction to it.
The only other source of stem cells at the moment is from embryos and this is fraught with ethical issues. "Our findings provide a foundation for producing functional liver cells for patients who suffer liver diseases and are in need of transplantation," said Professor Yoon-Young Jang, at Johns Hopkins Kimmel Cancer Center, in Maryland.
"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."
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, Jang says.
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 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. For the study, Prof Jang and colleagues generated human iPSCs from a variety of adult human cells, including liver cells, bone marrow stem cells and skin cells.
Next, they chemically induced the iPSCs to differentiate first into immature and then more mature liver cell types.
Using mice with human-like liver cirrhosis, the researchers then injected the animals with two 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 per cent, a rate similar to the engraftment rate for adult human liver cells at 11 per cent. Researchers also found the engrafted iPSCs worked well behaving like normal liver cells. Now the researchers hope to carry out trials in humans.
One concern has been the potential for embryonic stem cells or iPSCs to cause tumours, though no tumours formed in any of the transplanted mice during the seven months they were studied – the equivalent to more than 30 years in a human life.
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