Navigation Links
Scientists transform skin cells into functioning liver cells
Date:2/23/2014

SAN FRANCISCO, CAFebruary 23, 2014The power of regenerative medicine now allows scientists to transform skin cells into cells that closely resemble heart cells, pancreas cells and even neurons. However, a method to generate cells that are fully maturea crucial prerequisite for life-saving therapieshas proven far more difficult. But now, scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF), have made an important breakthrough: they have discovered a way to transform skin cells into mature, fully functioning liver cells that flourish on their own, even after being transplanted into laboratory animals modified to mimic liver failure.

In previous studies on liver-cell reprogramming, scientists had difficulty getting stem cell-derived liver cells to survive once being transplanted into existing liver tissue. But the Gladstone-UCSF team figured out a way to solve this problem. Writing in the latest issue of the journal Nature, researchers in the laboratories of Gladstone Senior Investigator Sheng Ding, PhD, and UCSF Associate Professor Holger Willenbring, MD, PhD, reveal a new cellular reprogramming method that transforms human skin cells into liver cells that are virtually indistinguishable from the cells that make up native liver tissue.

These results offer new hope for the millions of people suffering from, or at risk of developing, liver failurean increasingly common condition that results in progressive and irreversible loss of liver function. At present, the only option is a costly liver transplant. So, scientists have long looked to stem cell technology as a potential alternative. But thus far they have come up largely empty-handed.

"Earlier studies tried to reprogram skin cells back into a pluripotent, stem cell-like state in order to then grow liver cells," explained Dr. Ding, one of the paper's senior authors, who is also a professor of pharmaceutical chemistry at UCSF, with which Gladstone is affiliated. "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. 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."

This research, which was performed jointly at the Roddenberry Center for Stem Cell Research at Gladstone and the Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, involved using a 'cocktail' of reprogramming genes and chemical compounds to transform human skin cells into cells that resembled the endoderm. Endoderm cells are cells that eventually mature into many of the body's major organsincluding the liver.

"Instead of taking the skin cells back to the beginning, we took them only part way, creating endoderm-like cells," added Gladstone and CIRM Postdoctoral Scholar Saiyong Zhu, PhD, one of the paper's lead authors. "This step allowed us to generate a large reservoir of cells that could more readily be coaxed into becoming liver cells."

Next, the researchers discovered a set of genes and compounds that can transform these cells into functioning liver cells. And after just a few weeks, the team began to notice a transformation.

"The cells began to take on the shape of liver cells, and even started to perform regular liver-cell functions," said UCSF Postdoctoral Scholar Milad Rezvani, MD, the paper's other lead author. "They weren't fully mature cells yetbut they were on their way."

Now that the team was encouraged by these initial results in a dish, they wanted to see what would happen in an actual liver. So, they transplanted these early-stage liver cells into the livers of mice. Over a period of nine months, the team monitored cell function and growth by measuring levels of liver-specific proteins and genes.

Two months post-transplantation, the team noticed a boost in human liver protein levels in the mice, an indication that the transplanted cells were becoming mature, functional liver cells. Nine months later, cell growth had shown no signs of slowing down. These results indicate that the researchers have found the factors required to successfully regenerate liver tissue.

"Many questions remain, but the fact that these cells can fully mature and grow for months post-transplantation is extremely promising," added Dr. Willenbring, associate director of the UCSF Liver Center and the paper's other senior author. "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."


'/>"/>

Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534

Jeff Norris
JNorris@pubaff.ucsf.edu
415-476-8255

Gladstone Institutes
Source:Eurekalert


Related biology news :

1. Scientists unlock a microbial Pompeii
2. Scientists identify long distance scanner for DNA damage
3. A*STAR scientists discover proteins role in human memory and learning functions
4. Kids and insect scientists to meet in San Antonio
5. Wistar scientists develop gene test to accurately classify brain tumors
6. Ticks may cause double trouble, Stanford scientists find
7. Scientists call for new stewardship of the deep ocean: Earths last frontier
8. Thinking it through: Scientists seek to unlock mysteries of the brain
9. Scientists discover the mechanism of heart failure in fish exposed to oil spills
10. Harvard scientists find cell fate switch that decides liver, or pancreas?
11. U-M scientists & colleagues investigate the fiber of our being
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/31/2016)... 31, 2016  Genomics firm Nabsys has completed a ... Barrett Bready , M.D., who returned to the company ... technical leadership team, including Chief Technology Officer, John ... Steve Nurnberg and Vice President of Software and Informatics, ... Dr. Bready served as CEO of Nabsys ...
(Date:3/23/2016)... 23, 2016 ... Gesichts- und Stimmerkennung mit Passwörtern     ... MESG ), ein führender Anbieter digitaler ... mit SpeechPro zusammenarbeitet, um erstmals dessen Biometrietechnologie ... die Möglichkeit angeboten, im Rahmen mobiler Apps ...
(Date:3/22/2016)... PROVO and SANDY, Utah ... (NSO), which operates the highest sample volume laboratory in ... Tute Genomics and UNIConnect, leaders in clinical sequencing informatics ... the launch of a project to establish the informatics ... NSO has been contracted by the ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... Newly ... technologies, services and solutions to the healthcare market. The company's primary focus is ... manufacturing, sales and marketing strategies that are necessary to help companies efficiently bring ...
(Date:6/24/2016)... 24, 2016 Epic Sciences unveiled a ... susceptible to PARP inhibitors by targeting homologous recombination ... The new test has already been incorporated into ... cancer types. Over 230 clinical trials ... pathways, including PARP, ATM, ATR, DNA-PK and WEE-1. ...
(Date:6/23/2016)... 23, 2016   Boston Biomedical , an ... designed to target cancer stemness pathways, announced that ... Orphan Drug Designation from the U.S. Food and ... cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin is ... inhibit cancer stemness pathways by targeting STAT3, and ...
(Date:6/23/2016)... -- The Prostate Cancer Foundation (PCF) is pleased to announce 24 new ... prostate cancer. Members of the Class of 2016 were selected from a pool ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
Breaking Biology Technology: