(Press-News.org) The mechanisms that allow the liver to repair and regenerate itself have long been a matter of debate. Now researchers at University of California, San Diego School of Medicine have discovered a population of liver cells that are better at regenerating liver tissue than ordinary liver cells, or hepatocytes. The study, published August 13 in Cell, is the first to identify these so-called "hybrid hepatocytes," and show that they are able to regenerate liver tissue without giving rise to cancer. While most of the work described in the study was done in mouse models, the researchers also found similar cells in human livers.
Of all major organs, the liver has the highest capacity to regenerate -- that's why many liver diseases, including cirrhosis and hepatitis, can often be cured by transplanting a piece of liver from a healthy donor. The liver's regenerative properties were previously credited to a population of adult stem cells known as oval cells. But recent studies concluded that oval cells don't give rise to hepatocytes; instead, they develop into bile duct cells. These findings prompted researchers to begin looking elsewhere for the source of new hepatocytes in liver regeneration.
In this latest study, led by Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology, researchers traced the cells responsible for replenishing hepatocytes following chronic liver injury induced by exposure to carbon tetrachloride, a common environmental toxin. That's when they found a unique population of hepatocytes located in one specific area of the liver, called the portal triad. These special hepatocytes, the researchers found, undergo extensive proliferation and replenish liver mass after chronic liver injuries. Since the cells are similar to normal hepatocytes, but express low levels of bile duct cell-specific genes, the researchers called them "hybrid hepatocytes."
Meanwhile, many other research labs around the world are working on ways to use induced pluripotent stem cells (iPSCs) to repopulate diseased livers and prevent liver failure.
"Although hybrid hepatocytes are not stem cells, thus far they seem to be the most effective in rescuing a diseased liver from complete failure," said Joan Font-Burgada, PhD, postdoctoral researcher in Karin's lab and first author of the study.
While iPSCs hold a lot of promise for regenerative medicine, it can be difficult to ensure that they stop proliferating when their therapeutic job is done. As a result, iPSCs carry a high risk of giving rise to tumors. To test the safety of hybrid hepatocytes, Karin's team examined three different mouse models of liver cancer. They found no signs of hybrid hepatocytes in any of the tumors, leading the researchers to conclude that these cells don't contribute to liver cancer caused by obesity-induced hepatitis or chemical carcinogens.
"Hybrid hepatocytes represent not only the most effective way to repair a diseased liver, but also the safest way to prevent fatal liver failure by cell transplantation," Karin said.
INFORMATION:
Co-authors of this study also include Shabnam Shalapour, Atsushi Umemura, Koji Taniguchi, Mark A. Valasek, Maike Sander, and Hannah Carter, UC San Diego; Suvasini Ramaswamy, and Inder M. Verma, Salk Institute for Biological Studies; Brian Hsueh, Karl Deisseroth, and Li Ye, Howard Hughes Medical Institute and Stanford University; David Rossell, University of Warwick; Hayato Nakagawa, UC San Diego and University of Tokyo; and Janel L. Kopp, UC San Diego and University of British Columbia.
This research was funded by the National Institutes of Health, including the Superfund Research Program at the National Institute of Environmental Health Sciences (grants CA118165, CA155120, P30 CA014195-38, F32CA136124, ES010337, HL053670, AI048034, DK078803 and DK068471), California Institute for Regenerative Medicine, Rotary Foundation, Uehara Memorial Foundation, German Research Foundation, Japan Society for the Promotion of Science, Japanese Society of Gastroenterology, Tokyo Society of Medical Sciences, Kanae Foundation for the Promotion of Medical Science, Frances C. Berger Foundation, Leona M. and Harry B. Helmsley Charitable Trust and JDRF.
In what appears to be an unexpected challenge to a long-accepted fact of biology, Johns Hopkins researchers say they have found that ribosomes -- the molecular machines in all cells that build proteins -- can sometimes do so even within the so-called untranslated regions of the ribbons of genetic material known as messenger RNA (mRNA).
"This is an exciting find that generates a whole new set of questions for researchers," says Rachel Green, Ph.D., a Howard Hughes Medical Institute investigator and professor of molecular biology and genetics at the Johns Hopkins University ...
Researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and their collaborators have developed an experimental, nanoparticle-based vaccine against Epstein-Barr virus (EBV) that can induce potent neutralizing antibodies in vaccinated mice and nonhuman primates. Microscopic particles, known as nanoparticles, are being investigated as potential delivery vehicles for vaccines. The scientists' findings suggest that using a structure-based vaccine design and self-assembling nanoparticles to deliver a viral ...
In a recent study, restricting dietary fat led to body fat loss at a rate 68 percent higher than cutting the same number of carbohydrate calories when adults with obesity ate strictly controlled diets. Carb restriction lowered production of the fat-regulating hormone insulin and increased fat burning as expected, whereas fat restriction had no observed changes in insulin production or fat burning. The research was conducted at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. Results were published ...
Engineers from the University of Sheffield have developed a novel technique to predict when bearings inside wind turbines will fail which could make wind energy cheaper.
The method, published in the journal Proceedings of the Royal Society A and developed by Mechanical Engineering research student Wenqu Chen, uses ultrasonic waves to measure the load transmitted through a ball bearing in a wind turbine. The stress on wind turbine is recorded and then engineers can forecast its remaining service life.
When a bearing is subject to a load, its thickness is reduced by ...
Black-footed ferrets, a critically endangered species native to North America, have renewed hope for future survival thanks to successful efforts by a coalition of conservationists, including scientists at Lincoln Park Zoo, to reproduce genetically important offspring using frozen semen from a ferret who has been dead for approximately 20 years. The sire, "Scarface," as he is affectionately called by the team, was one of the last 18 black-footed ferrets to exist in the world in the 1980s. Eight kits, including offspring of Scarface, were born recently, significantly increasing ...
One of the more heartbreaking realities of Alzheimer's is the moment when a loved one struggling with the disease no longer fully recognizes a family member or close friend who is caring for them.
Now, new research from Washington University in St. Louis has identified a novel learning and memory brain network that processes incoming information based on whether it's something we've experienced previously or is deemed to be altogether new and unknown, helping us recognize, for instance, whether the face before us is that of a familiar friend or a complete stranger.
Forthcoming ...
Multigene testing of women negative for BRCA1 and BRCA2 found some of them harbored other harmful genetic mutations, most commonly moderate-risk breast and ovarian cancer genes and Lynch syndrome genes, which increase ovarian cancer risk, according to an article published online by JAMA Oncology.
Multigene panel genetic tests are increasingly recommended for patients evaluated for a predisposition to hereditary breast/ovarian cancer (HBOC). However, the rapid introduction of these tests has raised concerns because many of the tested genes are low- to moderate-risk genes ...
A study by researchers at three academic medical centers has shown that screening women with a suspected risk of hereditary breast or ovarian cancer for risk-associated genes other than BRCA1 and 2 provides information that can change clinical recommendations for patients and their family members. The report from a team led by a Massachusetts General Hospital (MGH) Cancer Center investigator is being published in the August issue of JAMA Oncology.
"The traditional approach has been to test most women with suspected hereditary risk for breast and/or ovarian cancer for ...
A University of Manchester study which followed up 38,415 people admitted to hospital with self-harm has, for the first time, investigated the association between the treatment patients receive in hospital and their subsequent risk of death.
Published in the Lancet Psychiatry, the study looked at adults who had self-harmed and attended five hospital emergency departments in Manchester, Oxford and Derby between 2000 and 2010. The researchers found that within 12 months, 261 had died by suicide and a further 832 had died from other causes.
The study also examined the ...
Organ transplant recipients are twice as likely to develop melanoma as people who do not undergo a transplant, and three times more likely to die of the dangerous skin cancer, suggests new research led by a Johns Hopkins Bloomberg School of Public Health student.
The findings, reported Aug. 13 in the Journal of Investigative Dermatology, suggest that the immunosuppressive medications that transplant recipients receive to keep them from rejecting their new organs -- especially the high doses administered at the time of transplant -- may make them more susceptible to later ...
