LyGenesis has been working towards liver organoid transplantation as a treatment for liver failure for some years now. Organs such as the liver, thymus, and a few others do not need to be in any specific place in the body to carry out many of their varied functions. Some of the vital work of the liver, for example, can be conducted in small organoids grown from liver cells transplanted into lymph nodes or other parts of the body that can act as stable bioreactors.
Even setting aside the possibility of growing functional liver organoids from patient cells or universal cell lines, it is worth noting that the old approach of harvesting donor livers could be used to create large numbers of organoids through the LyGenesis methology, and thereby help many more patients with liver disease than is presently possible through transplantation. In recent news, LyGenesis has now started a small clinical trial; we might hope that success for the company will spur the development of analogous approaches for other organs, such as the thymus.
'Mini liver' will grow in person's own lymph node in bold new trial
More than 50,000 people in the United States die each year with liver disease. In the end stage of the disease, scar tissue that has accumulated prevents the organ from filtering toxic substances in the blood, and can lead to infection or liver cancer. A liver transplant can help, but there is a shortage of organs: about 1,000 people in the United States die every year waiting for a transplant. Thousands more aren't eligible because they are too ill to undergo the procedure.
LyGenesis has been trialling an approach that could help people in this situation - and make use of donated livers that would otherwise go to waste because a person on the transplant waiting list with a compatible health profile hasn't materialized in time. The company's strategy delivers the donor cells through a tube in the throat, injecting them into a lymph node near the liver. Lymph nodes, which also filter waste in the body and are an important part of the immune system, are ideal for growing mini livers, because they receive a large supply of blood and there are hundreds of them throughout the body, so if a few are used to generate mini livers, plenty of others can continue to function as lymph nodes.
The treatment has so far worked in mice, dogs, and pigs. To test the therapy in pigs, researchers restricted blood flow to the animals' livers, causing the organs to fail, and injected donor cells into lymph nodes. Miniature livers formed within two months and had a cellular architecture resembling a healthy liver. Researchers even found cells that transport bile, a digestive fluid produced by the liver, in the mini livers of the pigs. In this case, they saw no build-up of bile acid, suggesting that the mini organs were processing the fluid.
The company aims to enroll 12 people into the phase II trial by mid-2025 and publish results the following year. The trial, which was approved by US regulators in 2020, will not only measure participant safety, survival time and quality of life post-treatment, but will also help to establish the ideal number of mini livers to stabilize someone's health. The clinicians running the trial will inject liver cells in up to five of a person's lymph nodes to determine whether the extra organs can boost the procedure's success rate. LyGenesis has ambitions beyond mini livers, too. The company is now testing similar approaches to grow kidney and pancreas cells in the lymph nodes of animals.
View the full article at FightAging
