About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Switching Capacity of Liver Cells

by Anjali Aryamvally on May 4, 2018 at 11:22 AM
Font : A-A+

Switching Capacity of Liver Cells

New study has discovered the mechanism behind an unusual form of tissue regeneration that may someday reduce the need for expensive and difficult-to-obtain organ transplants. The research team from Cincinnati Children's and the University of California San Francisco (UCSF) made the discovery by studying a rare liver disease called Alagille syndrome.

The team's findings, published in the journal Nature, show that when disease or injury causes a shortage in one critical type of liver cell, the organ can instruct another type of liver cell to change identities to provide replacement supplies.

Advertisement


This discovery was made in mice but in years to come may lead to a viable treatment for human disease. If ongoing follow-up studies succeed, the medical world may gain an alternative method for repairing tissue damage that does not require manipulating stem cells to grow organs from scratch in a lab dish.

"We have known for a long time that the liver has more ability to regenerate than other organs. Only recently have we had the tools to study this ability in depth. Now we have a high-level understanding," says Stacey Huppert, PhD, a developmental biologist in the Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's, and one of two leading co-authors of the paper.
Advertisement

"Our study shows that the form and function of hepatocytes--the cell type that provides most of the liver's functions--are remarkably flexible. This flexibility provides an opportunity for therapy for a large group of liver diseases," says Holger Willenbring, MD, PhD, the study's other senior co-author and a member of the Department of Surgery, the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and the Liver Center at UCSF.

What is Alagille syndrome?

Alagille syndrome (ALGS) is a rare, inherited genetic disorder due to deficiencies in the Notch pathway, which plays an important role in cell development. ALGS is best known for disrupting the liver's plumbing system, which consists of tubes called bile ducts that deliver bile made in the liver to the intestine. The disorder occurs in about 1 in 30,000 people, and in most cases, the problems caused by the condition emerge during infancy or early childhood.

The extent of the condition can range from having too few or too narrow bile ducts to missing all bile ducts in the liver. As a result, the bile that normally helps the body digest fat and carry away toxins backs up inside the liver where it causes severe damage. In many patients with ALGS, bile duct function can be managed and sustained. However, up to 50 percent of patients eventually need a liver transplant, often during childhood.

A Quicker Method of Self-Repair

Every day, the liver takes a beating as it processes everything from medications to alcohol consumption. All these "insults" have prompted the liver to develop a rapid healing ability that does not rely on stem cells, the co-authors say.

"In addition to making more of themselves, liver cells can switch their identity to produce a liver cell type that is lost or, in the case of severe ALGS, never formed," Willenbring says.

"Previous research has detected adaptive reprogramming in other organs, but it typically involves only a few cells at a time. Our study shows that cells switch their identity at a massive rate in the liver," Huppert says.

Discovering this phenomenon and learning how it works took nearly five years. The team included co-first authors Johanna Schaub and Simone Kurial from UCSF and Kari Huppert from Cincinnati Children's.

The researchers generated mice that lack cholangiocytes, the type of liver cell that forms bile ducts. Like patients with severe ALGS, these mice quickly developed signs of liver injury. However, over time the mice's symptoms improved because hepatocytes converted into cholangiocytes and formed fully functional bile ducts.

In July 2017, another study published in Nature reported that cholangiocytes can become hepatocytes if their ability to regenerate is impaired. Viewed together, the two studies suggest that switching of cell identity is the main backup mechanism for liver repair.

The new study further shows that the Notch pathway, which is essential for forming bile ducts but defective in patients with ALGS, can be replaced by another pathway. This process is regulated in the injured liver by transforming growth factor beta (TGFβ), a protein that controls cell growth. This discovery is a vital step in identifying targets for therapies that might control this process.

Next Steps

Now the research team is working to determine the precise set of proteins, called transcription factors, that work together to carry out the identity-switching process.

"Using transcription factors to make bile ducts from hepatocytes has potential as a safe and effective therapy," Willenbring says. "With our finding that an entire biliary system can be 'retrofitted' in the mouse liver, I am encouraged that this eventually will work in patients."

In addition to developing a therapy for ALGS, the team hopes to determine whether liver cell switching can benefit other types of liver disease.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
Top 7 Benefits of Good Oral Hygiene
Healthy and Safer Thanksgiving 2021
Long-Term Glycemic Control - A Better Measure of COVID-19 Severity
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Hepatitis A Parkinsons Disease Surgical Treatment Liver Wilson's Disease Milk Thistle Current Treatments for Liver Cancer Fatty Liver Disease: A Growing Health Problem in India Living Donor Liver Transplant: What Are the Risks? 

Recommended Reading
Inflammation Required for Smell Tissue Regeneration
In patients with chronic sinusitis, the regeneration of olfactory tissue requires some of the same ....
Novel Genomic Tool Spurs Deeper Understanding of Tissue Regeneration
A catalogue of every active gene in a variety of tissues in the axolotl has been assembled by ......
Genetic Elements That Drive Tissue Regeneration Uncovered by researchers
Researchers have found that genes important for regeneration in salamanders or zebra fish also have ...
Liver Tissue Regeneration in Mammals is Actually Possible
The liver is unique among human solid organs in its robust regenerative capability. A healthy liver ...
Current Treatments for Liver Cancer
Current Treatments for Liver Cancer (also known as hepatoma or hepatocellular carcinoma) can result ...
Fatty Liver Disease: A Growing Health Problem in India
Non alcoholic fatty liver disease (NAFLD) is the leading cause of liver dysfunction worldwide and is...
Hepatitis A
Hepatitis A is the most benign of the hepatitis viruses and usually has no long term side effects. H...
Living Donor Liver Transplant: What Are the Risks?
The risk of dying as a result of a living donor liver segment removal is between 0.2-2.0%. The risk ...
Milk Thistle
Milk Thistle is a resourceful natural plant which has many medicinal benefits. In herbal medication ...
Wilson's Disease
This is a rare inherited systemic disorder of copper metabolism, affecting the liver mainly before o...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use