Mature, functioning liver cells made from skin cells

Date: Feb-24-2014There have been several reports in recent years of scientists reprogramming skin

cells so they transform into cells that are similar to cells from other organs, such as the heart,

the pancreas and even brain cells. However, these have fallen short of producing mature, fully functioning versions of organ

cells - essential if they are to be of any use in life-saving regenerative medicine.

Now, a new study reported in Nature shows how it may be possible, with a new method,

to transform skin cells into mature, fully functioning liver cells that are practically

identical to native cells in liver tissue.

Not only this, but the new cells also flourish on their own, even after being transplanted

into the livers of animals with engineered liver failure.

The results raise hopes for millions of people who have or who are at risk of developing liver

failure. Currently, their only option is a liver transplant.

The breakthrough is the work of scientists at the Gladstone Institutes and the University of

California, San Francisco (UCSF).

In their study, they explain how previous attempts failed to get stem cell-derived

liver cells to survive once they were transplanted into living liver tissue.

Co-lead author Sheng Ding, a professor of pharmaceutical chemistry at UCSF, says:

"Earlier studies tried to reprogram skin cells back into a pluripotent, stem cell-like state

in order to then grow liver cells. However, 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."

They took the skin cells back to an intermediate, rather than fully pluripotent state

The researchers overcame this problem by taking the skin cells to an intermediate state instead of all

the way back to pluripotent state. Pluripotent stem cells are cells that have the potential to

mature into almost any other kind of cell in the body.

To achieve their result, Prof. Ding and colleagues used a "cocktail" of genes

and molecules to reprogram human skin cells to resemble endoderm cells - cells that

have the potential to mature into the tissue of major organs, including the liver.

The researchers found by taking the skin cells back only to this intermediate state, they

were able to generate a large reservoir of cells that could then be more easily coaxed into

transforming into liver cells.

To complete this second step, they found another set of genes and molecules that could

reprogram the endoderm-like cells into fuctioning liver cells.

They could see the transformation a few weeks after the reprogramming, as the paper's other

co-lead author, Dr. Milad Rezvani of UCSF, explains:

"The cells began to take on the shape of liver cells, and even started to perform regular

liver-cell functions. They weren't fully mature cells yet - but they were on their way."

Transplanted cells still growing 9 months later

Up to this point, the researchers were working with cultured cells in petri dishes. For the

next stage, they carried out tests in live mice, engineered to have a human form of liver

failure.

They transplanted the early-stage (human) liver cells into the livers of the mice and kept an

eye on them for 9 months.

Two months after transplant, there was a boost in levels of human liver proteins, a sign that

the cells were maturing into functioning liver cells.

Plus, at the end of the 9 months, cell growth showed no sign of slowing down.

The results are a good indication that the new method can successfully regenerate liver

tissue, say the researchers.

One of the senior authors, Dr. Willenbring, associate director of the UCSF Liver Center, says

there are still many questions to answer, but the fact the cells can mature and keep growing

for 9 months after transplant is "extremely promising." He adds:

"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."

The California Institute for Regenerative Medicine, the National Institutes of

Health, the German Academic Exchange Service, and the Society of University Surgeons financed the study.

Medical News Today recently reported on another study led by the Genome

Institute of Singapore, where scientists made pure precursor liver and pancreas

cells from stem cells, overcoming some of the perplexing challenges of coaxing stem cells to

transform into highly sought populations of pure tissue-specific cells.

Written by Catharine Paddock PhD




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