Skin cells have been transformed into human liver cells that are not only able to function within an organ, but do so inside another species and continue to operate in an animal with liver failure.
The capacity to cause easily available cells, such as those from skin, to transform into those of organs such as the pancreas, or even into neurons, has generated great hope and hype. Nevertheless what has been done is generally several steps short of being something that could be transplanted into a body when the old organ fails.
One of the necessary steps is to get cells to survive when transplanted into the body. A team from the Gladstone Institutes and the University of California San Francisco have announced success in this regard in Nature, turning skin cells into cells they describe as “virtually indistinguishable” from native liver cells.
Although the liver is the only human internal organ capable of regenerating itself, this capacity is not unlimited. Millions of people suffer liver damage from everything from too much alcohol or a paracetamol overdose to diseases such as hepatitis C. Livers for transplantation are in very short supply.
“Earlier studies tried to reprogram skin cells back into a pluripotent, stem cell-like state in order to then grow liver cells,” says Dr. Sheng Ding, one of the paper’s senior authors, and professor of pharmaceutical chemistry at UCSF. Pluripotent stem cells are those with the potential to form into all three of the primary categories of body cells. However, pluripotent cells don't always make the step to the desired organ.
“Generating these so-called induced pluripotent stem cells, or iPS cells, and then transforming them into liver cells wasn’t always resulting in complete transformation,” says Ding. “So we thought that, rather than taking these skin cells all the way back to a pluripotent, stem cell-like state, perhaps we could take them to an intermediate phase.”
Cells in this intermediate phase, the endoderm, are part way to becoming constituents of the body's major organs. “The cells began to take on the shape of liver cells, and even started to perform regular liver-cell functions,” says UCSF's Dr Scholar Milad Rezvani, the paper’s other lead author. “They weren’t fully mature cells yet—but they were on their way.”
The failure of cells to proliferate in living animals when transplanted has, according to the paper's authors, “hampered efforts to recreate human liver diseases in mice.” Consequently, transplanting the cells to mice was not only a stepping stone to lifesaving transplants for humans, but a way to close in on better research tools.
Nine months after transplantation the cells continued to function and grow within the mouse livers, indicating their operation through the presence of human proteins, not normally produced in mouse livers.
“Many questions remain, but the fact that these cells can fully mature and grow for months post-transplantation is extremely promising,” adds Dr. Willenbring, associate director of the UCSF Liver Center “In the future, our technique could serve as an alternative for liver-failure patients who don’t require full-organ replacement, or who don’t have access to a transplant due to limited donor organ availability.”