Scientists Uncover Cell Responsible for Repairing Liver Tissue

The AHA! Team — Mon, 06 May 2024 18:05:40 +0000

University College London via News-Medical – A type of cell responsible for repairing damaged liver tissue has been uncovered for the first time by a team of scientists, including Professor Rajiv Jalan (UCL Liver & Digestive Health). The study, published in Nature, showed how these new-found cells migrate to the site of damage, providing new insights into the way the liver heals itself. The authors say the findings could spur the development of new therapies that harness the liver’s unique capacity to regenerate. During acute liver failure, the organ’s ability to repair and regenerate is often overwhelmed, with patients requiring an emergency liver transplant to regain liver function. Scientists from the University of Edinburgh studied human liver tissue from patients with acute liver failure for signs of cell proliferation and regeneration following the rapid loss of liver function. They found that a significant proportion of cells retained the ability to multiply. There were, however, still substantial areas of damage in the patients’ livers, suggesting that processes other than cell proliferation are critical during regeneration. The research team profiled the genes within every liver cell in both healthy and regenerating human liver tissue to better understand the regeneration process, using a technique called single-cell RNA sequencing. The findings uncovered a previously undetected population of wound-healing liver cells that emerge during human liver regeneration to aid recovery. Working with University of Glasgow scientists at the Cancer Research UK Scotland Institute, the team used special imaging techniques in mice to view the wound-healing cells in action. Researchers from the UCL Institute for Liver & Digestive Health and the Royal Free Hospital then provided important clinical validation of the novel mechanism of liver repair in humans. “We investigated whether the ‘liver repair’ mechanisms that the team from Edinburgh and Glasgow discovered in animal models also occurred in humans, and found that the mechanisms were present in patients with severe acute indeterminate hepatitis. This provides evidence that the observations made in the study are likely to be clinically relevant for the treatment of liver diseases in humans.” -Professor Rajiv Jalan, UCL Liver & Digestive Health During liver regeneration, so-called leader cells appear at the edge of the healthy tissue, dragging the tissue together to close the wound – similarly to how skin heals after a cut. Imaging also revealed that the population of healing liver cells appears before cell proliferation begins. Widespread infection is a major concern following acute liver failure. Bacteria from the gut can escape into the liver when the liver is damaged. This can lead to sepsis if the liver is unable to clear the infection. The liver may prioritise the healing of wounds before cell proliferation to restore the gut-liver barrier and prevent the spread of bacteria, experts say. Professor Neil Henderson, principal investigator of the study from the University of Edinburgh’s Centre for Inflammation Research, said: “Cutting-edge technologies have allowed us to study human liver regeneration in high definition for the first time, facilitating the identification of a cell type that is critical for liver repair. “We hope that our findings will accelerate the discovery of much-needed new treatments for patients with liver disease.” The research team also included scientists from the Universities of Birmingham, Cambridge and Texas, and the United States Acute Liver Failure Study Group network. This work was funded by Wellcome. Journal reference: Matchett, K. P., et al. (2024). Multimodal decoding of human liver regeneration. Nature. doi.org/10.1038/s41586-024-07376-2. To read the original article click here.

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Pig-To-Human Transplants Come A Step Closer With New Test

AHA Publisher — Wed, 27 Oct 2021 07:00:18 +0000

Carla K Johnson via CBN News – Scientists temporarily attached a pig’s kidney to a human body and watched it begin to work, a small step in the decades-long quest to one day use animal organs for life-saving transplants. Pigs have been the most recent research focus to address the organ shortage, but among the hurdles: A sugar in pig cells, foreign to the human body, causes immediate organ rejection. The kidney for this experiment came from a gene-edited animal, engineered to eliminate that sugar and avoid an immune system attack. Surgeons attached the pig kidney to a pair of large blood vessels outside the body of a deceased recipient so they could observe it for two days. The kidney did what it was supposed to do — filter waste and produce urine — and didn’t trigger rejection. “It had absolutely normal function,” said Dr. Robert Montgomery, who led the surgical team last month at NYU Langone Health. “It didn’t have this immediate rejection that we have worried about.” This research is “a significant step,” said Dr. Andrew Adams of the University of Minnesota Medical School, who was not part of the work. It will reassure patients, researchers and regulators “that we’re moving in the right direction.” The dream of animal-to-human transplants — or xenotransplantation — goes back to the 17th century with stumbling attempts to use animal blood for transfusions. By the 20th century, surgeons were attempting transplants of organs from baboons into humans, notably Baby Fae, a dying infant, who lived 21 days with a baboon heart. With no lasting success and much public uproar, scientists turned from primates to pigs, tinkering with their genes to bridge the species gap. Pigs have advantages over monkeys and apes. They are produced for food, so using them for organs raises fewer ethical concerns. Pigs have large litters, short gestation periods and organs comparable to humans. Pig heart valves also have been used successfully for decades in humans. The blood thinner heparin is derived from pig intestines. Pig skin grafts are used on burns and Chinese surgeons have used pig corneas to restore sight. In the NYU case, researchers kept a deceased woman’s body going on a ventilator after her family agreed to the experiment. The woman had wished to donate her organs, but they weren’t suitable for traditional donation. The family felt “there was a possibility that some good could come from this gift,” Montgomery said. Montgomery himself received a transplant three years ago, a human heart from a donor with hepatitis C because he was willing to take any organ. “I was one of those people lying in an ICU waiting and not knowing whether an organ was going to come in time,” he said. Several biotech companies are in the running to develop suitable pig organs for transplant to help ease the human organ shortage. More than 90,000 people in the U.S. are in line for a kidney transplant. Every day, 12 die while waiting. The advance is a win for Revivicor, a subsidiary of United Therapeutics, the company that engineered the pig and its cousins, a herd of 100 raised in tightly controlled conditions at a facility in Iowa. The pigs lack a gene that produces alpha-gal, the sugar that provokes an immediate attack from the human immune system. In December, the Food and Drug Administration approved the gene alteration in the Revivicor pigs as safe for human food consumption and medicine. But the FDA said developers would need to submit more paperwork before pig organs could be transplanted into living humans. “This is an important step forward in realizing the promise of xenotransplantation, which will save thousands of lives each year in the not-too-distant future,” said United Therapeutics CEO Martine Rothblatt in a statement. Experts say tests on nonhuman primates and last month’s experiment with a human body pave the way for the first experimental pig kidney or heart transplants in living people in the next several years. Raising pigs to be organ donors feels wrong to some people, but it may grow more acceptable if concerns about animal welfare can be addressed, said Karen Maschke, a research scholar at the Hastings Center, who will help develop ethics and policy recommendations for the first clinical trials under a grant from the National Institutes of Health. “The other issue is going to be: Should we be doing this just because we can?” Maschke said. To read the original article click here.

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Scientists Uncover Cell Responsible for Repairing Liver Tissue

Pig-To-Human Transplants Come A Step Closer With New Test