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Researchers Investigate New Treatments for Leading Cancers

WASHINGTON — January 02, 2017 12:56 AM Carol Pearson Scientists are investigating new ways of treating people with liver cancer. The methods range from developing an artificial liver, to seeing if genetically-modified pigs can produce organs compatible with humans. For those who have liver cancer, their only cure lies in a liver transplant or removal of the cancerous part of the organ. Both require major surgery. And, patients who get a transplant will need to take immuno-suppressant drugs for the rest of their lives. However, scientists are working on a new approach that is minimally invasive. With both chemotherapy and radiation, healthy cells around the tumor are damaged. But this approach involves the use of natural, non-toxic chemical compounds from plants. Kattesh Katti, a professor at the University of Missouri School of Medicine, led a study that used nanotechnology to target and destroy precancerous tumor cells in the livers of mice and in in-vitro human cells. “It sounds like a fairy tale, but we are really in advanced stages in terms of tumor treatment, in terms of disease diagnostics," said Katti. Katti's work involved very small particles of gold encapsulated in a protective stabilizer from an acacia tree. The particles attract precancerous and malignant cells, which are far more susceptible to lower levels of heat than healthy cells. “The patient will be administered with these nano particles. Within a couple of hours, the patient will be treated with lasers, and then the patient can go home. So, there is no radioactivity. There is no toxic waste. There is no toxicity, systemic toxicity, to the patient,” said Katti. Katti said the cost of treatment will be low because one gram of gold can be used to treat 50 [...]

As CIRM opens world’s largest stem cell bank, scientists ready their research

Sep 1, 2015 A $32 million public-private bank — where California researchers collect stem cells and scientists from around the world can make withdrawals — officially opened Tuesday with the aim of accelerating the use of engineered stem cells to tackle a wide range of diseases. The bank, funded by the California Institute for Regenerative Medicine and located at Novato's Buck Institute for Research on Aging, already is making 300 induced pluripotent stem cell lines available to researchers studying heart, lung, liver and blinding eye diseases as well as epilepsy, autism, cerebral palsy and Alzheimer's Disease. Officials at San Francisco-based CIRM, which is the state's stem cell research funding agency, said the bank is the largest in the world, based on the number of donors, and will have 750 cell lines by February. But it also is a big win for CIRM as critics push the agency to show some bang from the more than $2 billion it has spent since California voters in 2004 approved selling $3 billion in bonds for stem cell research. CIRM in March 2013 approved spending $32 million to create the bank of induced pluripotent stem cells, which are "mature" cells, such as the skin, that are manipulated to return to their embryonic state. At that point, the bank can coax the cells back to a mature state but as heart, liver, skin or any other organ. The process — with major contributions from Nobel Prize winner Shinya Yamanaka of Kyoto University, the Gladstone Institutes and the University of California, San Francisco — means that a researcher isn't required to get true embryonic stem cells from the brain of an autism patient, for example, and can instead get skin cells [...]

Newly Discovered Cells Regenerate Liver Tissue Without Forming Tumors

Hybrid hepatocytes proliferate and replenish liver mass after chronic liver injuries in mice August 13, 2015  |  Heather Buschman, PhD 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. Hybrid hepatocytes (green) expand during chronic liver damage. 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 [...]

UTSW Researchers Find Molecule Able to Accelerate Tissue Regeneration Upon Injury

July 20, 2015 Patricia Silva - A study recently published in the renowned journal Science revealed a molecule able to accelerate tissue regeneration after bone marrow transplantation and other tissue injuries in mice. The study is entitled “Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration” and was led by researchers at the University of Texas Southwestern Medical Center, Case Western Reserve University and the University of Kentucky. Tissue regeneration is an important feature in several clinical settings including diseases, injury, and certain treatments such as the recovery of the hematopoietic system after bone marrow transplantation, a common treatment for leukemia patients. Because of this, there is interest in developing agents able to accelerate the tissue regeneration process, especially if they can benefit several organ systems. Researchers have now discovered a molecule that may accelerate tissue regeneration. The prostaglandin PGE2 is a signaling factor that is involved in the expansion of several types of tissue stem cells, contributing to tissue regeneration. In the study, researchers identified a prostaglandin-degrading enzyme known as 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and investigated its potential role as a negative regulator of tissue regeneration. The team used mice with depleted 15-PGDH in order to determine the role of this enzyme in controlling PGE2 levels and the tissue repair capacity in several organs. Researchers also developed a potent small-molecule inhibitor against 15-PGDH – SW033291. Researchers found that 15-PGDH–deficient mice have a twofold increase in PGE2 levels in different tissues (including bone marrow, colon and liver) in comparison to wild-type mice, an increased capability to respond to cell damage in these particular tissues, and an enhanced hematopoietic capacity. Remarkably, by inhibiting 15–PGDH with SW033291, researchers found that it was possible to rescue the damaged hematopoietic [...]

Organ transplant rejection may not be permanent

Organ transplant rejection in previously tolerant hosts does not lead to permanent immune memory, mouse study shows July 7, 2015 Rejection of transplanted organs in hosts that were previously tolerant may not be permanent, report scientists from the University of Chicago. Using a mouse model of cardiac transplantation, they found that immune tolerance can spontaneously recover after an infection-triggered rejection event, and that hosts can accept subsequent transplants as soon as a week after. This process depends on regulatory T-cells, a component of the immune system that acts as a "brake" for other immune cells. The findings, published online in Nature Communicationson July 7, support inducing immune tolerance as a viable strategy to achieve life-long transplant survival. "Transplantation tolerance appears to be a resilient and persistent state, even though it can be transiently overcome," said Anita Chong, PhD, professor of transplantation surgery at the University of Chicago and co-senior author of the study. "Our results change the paradigm that immune memory of a transplant rejection is invariably permanent." To prevent transplant rejection in patients with end-stage organ failure, a lifelong regimen of immune-suppressing drugs is almost always required. While difficult to achieve, immune tolerance -- in which a transplanted organ is accepted without long-term immunosuppression -- can be induced in some patients. However, rejection can still be triggered by events such as bacterial infection, even after long periods of tolerance. It has been assumed that the immune system remembers rejection and prevents future transplants from being tolerated. Chong and her colleagues have previously shown in mice that certain bacterial infections can disrupt tolerance and trigger rejection of an otherwise stable transplant. As they further studied this phenomenon, they made a surprising observation. Infection-triggered rejection caused [...]

First steps in basic biological process that could be harnessed to make therapeutic cells

April 16, 2015Pioneer factor binding chromosomes is shown. Credit: Kenneth S. Zaret, Ph.D., Perelman School of Medicine, University of PennsylvaniaUnderstanding the molecular signals that guide early cells in the embryo to develop into different types of organs provides insight into how tissues regenerate and repair themselves. By knowing the principles that underlie the intricate steps in this transformation, researchers will be able to make new cells at will for transplantation and tissue repair in such situations as liver or heart disease. Now, investigators at the Perelman School of Medicine at the University of Pennsylvania are able to explain how cell identity changes occur at the very beginning of the process. "During my scientific life, I've been fascinated by how early cells make 'decisions' to turn on one genetic program and exclude others," says Kenneth S. Zaret, PhD, director of the Institute for Regenerative Medicine and a professor of Cell and Developmental Biology. Zaret and postdoctoral fellow Abdenour Soufi, PhD, led a team that describes this research, which appeared online this week ahead of print in Cell. Soufi is now at the MRC Centre for Regenerative Medicine, University of Edinburgh. What they found could be applied to guiding cells to fates proposed by scientists for a wide variety of biomedical contexts, for example, to better understand molecular changes in the early embryo after fertilization, when one cell type morphs into another. Another application could be to directly change one cell type into another for therapeutic purposes, for example transforming a skin cell directly into a liver, blood, or heart cell. Tightly Packed DNA in each cell is two meters long and 20 atoms wide. All of this genetic material needs to be wound into the nucleus [...]

MSU team publishes findings about backup system that helps sustain liver during crisis

21/03/2015 02:35:00 By Evelyn Boswell, MSU News Service - BOZEMAN – Scientists from Montana State University and Sweden have discovered an antioxidant system that helps sustain the liver when other systems are missing or compromised. Like a generator kicking in when the power fails or an understudy taking the stage when a lead actor is sick, the newly found system steps up during a crisis. It’s fueled by methionine, an amino acid that can’t be manufactured in the body and doesn’t come from herbal teas or supplements. People get it only by eating protein. “This is an important finding,” said Ed Schmidt, a professor in MSU’s Department of Microbiology and Immunology and co-author of a newly published study in Nature Communications. “It tells us about humans and all living things. It’s an alternative way to maintain the balance you need in your cells to be alive.” Schmidt and his collaborators at the Karolinska Institute published their findings March 20 in Nature Communications, a scientific journal affiliated with the prestigious international journal, Nature. Nature Communications covers all topics in physics, chemistry, earth sciences and biology. The Karolinska Institute is one of Europe’s largest and most distinguished medical universities. Some vitamins and supplements act as antioxidants, Schmidt said. They help protect cells from the damage that can lead to aging, cancers and inflammatory diseases. However, vitamins and supplements can’t replace two known natural systems in liver cells: the thioredoxin and glutathione systems. To investigate further, Schmidt’s lab generated mice whose livers lacked key components of both systems. The mice were not robust. They were on the brink of failure, Schmidt said. And yet they survived. Investigating the mystery, the researchers found the third antioxidant system and said it [...]

Rebooting Cell Programming Can Reverse Liver Failure, Says Children’s Hospital/Pitt Study

PITTSBURGH, March 16, 2015 – It might be possible to heal cirrhotic liver disease by rebooting the genes that control liver cell function, according to researchers at Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine. If validated in human studies, the game-changing strategy, described today in the online version of the Journal of Clinical Investigation, could potentially treat patients who are too sick for liver transplantation and, in the future, reduce the need for transplants. The project grew out of the observation that not everyone who develops cirrhosis, or scarring of the liver, progresses to liver failure and its life threatening complications, explained Ira Fox, M.D., professor of surgery, Pitt School of Medicine, and director of the Center for Innovative Regenerative Therapies at Children's Hospital and the McGowan Institute for Regenerative Medicine. “Even with the large amount of scar tissue that comes with cirrhosis, there should be enough cells left to carry out the normal functions of the liver,” Dr. Fox said. “So when the liver fails, it is the liver cells themselves that aren’t working properly. In this study, we demonstrate what has caused the problem, and more importantly, a way to repair it.” His team developed a rat model of liver disease that mimics the form of human cirrhosis that progresses to organ failure. In previous work, they found that liver cells taken from animals with cirrhosis, but no liver failure, immediately functioned properly when transplanted into another animal. But cells transplanted from animals with both cirrhosis and liver failure did not function normally at first, indicating that both the liver cells and the liver tissue environment were damaged. The researchers then compared the genes in the [...]

With Liver Donors in Short Supply, Cell Transplants Offer New Options

For many liver disease patients, implantation of a few new cells from a healthy organ may buy time or avoid a full transplant altogether February 17, 2015 |By Jessica Wapner A new approach may provide a stopgap or, in time, an entirely new alternative. Called hepatocyte transplantation, the technique replaces approximately 10 percent of the liver with healthy cells from a deceased donor. Credit: Nephron via Wikimedia CommonsEvery year more than 6,000 people with liver disease or facing liver failure receive whole-organ transplantations in the U.S. Although the procedure is relatively safe and effective, problems remain: Demand outpaces supply; whereas the current U.S. waiting list stands at more than 15,000 only about 6,000 donations are made yearly. The procedure can cost more than $300,000 and immunosuppressants, drugs that prevent the immune system from rejecting the new organ, can lead to dangerous infections and uncontrolled bleeding. A new approach may provide a stopgap or, in time, an entirely new alternative. Called hepatocyte transplantation, the technique replaces approximately 10 percent of the liver with healthy cells from a deceased donor. The patient’s organ is not removed, decreasing recovery time, complications and cost. With fewer than 150 U.S. recipients so far, the approach is in its early days. If certain hurdles—such as the limited supply of cells and limited space in the patient’s liver—are overcome, hepatocyte transplantation may become an option for many liver disease sufferers. Some metabolic disorders, normally treated with whole-organ transplant, could be corrected with this less-intensive approach instead. For patients facing acute liver failure, hepatocyte transplantation could help their livers function until they recover. Some diseases for which liver transplantation would not be appropriate, such as amino acid disorders like phenylketonuria (PKU) and tyrosinemia, [...]

Tonsil stem cells could someday help repair liver damage without surgery

Medical News Today, Source: American Chemical Society ~ October 17, 2014 The liver provides critical functions, such as ridding the body of toxins. Its failure can be deadly, and there are few options for fixing it. But scientists now report in the journal ACS Applied Materials & Interfaces a way to potentially inject stem cells from tonsils, a body part we don't need, to repair damaged livers - all without surgery. Byeongmoon Jeong and colleagues point out that currently, the only established method for treating liver failure or severe cases of liver disease is complete or partial transplantation. But the need is much greater than the number of available organs. Plus, surgery has inherent risks and a hefty price tag. A promising alternative in development is transplanting liver cells. One such approach involves using adult stem cells to make liver cells. Stem cells from bone marrow could be used, but they have limitations. Recently, scientists identified another source of adult stem cells that could be used for this purpose - tonsils. Every year, thousands of surgeries are performed to remove tonsils, and the tissue is discarded. Now it could have a new purpose, but scientists needed a way to grow them on a 3-D scaffold that mimics real liver tissue. Jeong's team set out to do just that. The researchers encapsulated tonsil-derived stem cells in a heat-sensitive liquid that turns into a gel at body temperature. They added substances called growth factors to encourage the stem cells to become liver cells. Then, they heated the combination up to a normal body temperature. The result was a 3-D, biodegradable gel that contained functioning liver cells. The researchers conclude that the same process has promise - with [...]