Lifesaving liver patch can help repair and prevent liver disease

Researchers have unveiled a groundbreaking patch designed to aid in the regeneration of liver tissue, as reported in the Biotechnology Journal.

This advanced patch is crafted from a blend of decellularized liver matrix, a special liver growth factor, and an anticoagulant. In laboratory experiments with liver cells, the patch showed remarkable results, helping the cells recover their function after being damaged by toxins.

When tested on rats, the patch, applied to the liver and surrounding gut, significantly improved recovery from liver fibrosis. The treated rats exhibited less scarring and reduced inflammation.

“The hepatic patch made from the decellularized liver matrix has proven its capability to restore liver function and curb inflammation in fibrotic livers,” explained Dr. Yung-Te Hou from National Taiwan University, the lead author of the study. “This innovative approach holds tremendous promise for treating a range of liver conditions, from the relatively mild fatty liver to severe diseases like liver cirrhosis.”

Liver cirrhosis, a severe outcome of chronic liver inflammation, replaces normal liver tissue with regenerative nodules, disrupting liver function and leading to potential liver failure.

Despite ongoing research into treatments for advanced liver disease, current options, aside from liver transplantation, mainly provide symptomatic relief through lifestyle changes like diet, exercise, and weight loss. These methods, however, are not very effective in controlling the excessive ECM production by HSCs and may sometimes worsen fibrosis.

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Liver transplantation remains the most reliable treatment for severe liver disease, but the demand far exceeds the supply of donor livers. Tragically, about 10% of patients die while waiting for a transplant due to the progression of their condition.

If a transplant is performed before the disease becomes too advanced, the success rate is high, ranging from 85% to 95%. However, the procedure carries significant risks, including a 40% to 75% chance of complications, some of which can be fatal.

Conventional cell therapy shows potential in treating fibrosis and cirrhosis but faces significant hurdles. One major challenge is the limited availability and poor viability of hepatocytes, the primary cells of the liver. Effective therapy would require an enormous number of these cells (over 10 billion), alongside other critical non-parenchymal cells like liver sinusoidal endothelial cells, Kupffer cells, and cholangiocytes.

Stem cells, known for their ability to self-renew and differentiate into various cell types, offer hope. However, the use of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) carries risks, including the potential formation of teratomas, which are tumors made up of different types of tissue. Although pre-differentiating these stem cells into more specialized forms might mitigate this risk, the process is lengthy and resource-intensive, limiting its clinical application.

An alternative to cell therapy is liver tissue engineering, which aims to create functional liver constructs that replicate the organ’s structure and function. These bioengineered constructs need to be integrated into the liver at the site of injury to be effective, rather than being implanted in other parts of the body.

One promising approach in tissue engineering is the development of cell sheet-based hepatic patches. These patches preserve the connections between cells and their ECM, potentially improving the retention and functionality of the transplanted cells.

Recent studies highlight the therapeutic potential of hepatic patches. Kim and colleagues simulated ECM conditions to rapidly differentiate human primary hepatocytes into progenitor cells and then into functional liver cells. These cells were used to create hepatic patches that, when transplanted onto injured mouse livers, facilitated successful liver restoration.

In another study, Yi and his team developed patches for drug delivery using a combination of materials that extended the release of the drug, 5-fluorouracil, used in treating pancreatic cancer. This approach achieved the desired pharmacokinetics and demonstrated the versatility of patch-based treatments.

Nobakht Lahrood and collaborators created hepatic patches using decellularized liver matrix (DLM), a natural biomaterial, and seeded them with a combination of human liver cancer cells, mesenchymal stem cells, and endothelial cells. These patches, when applied to damaged mouse livers, promoted liver restoration.

However, challenges remain, including the limited availability of scalable and renewable cell sources and the potential for cell sheets to contract and shrink due to changes in cell structure after detachment from their surfaces.

The new study builds on previous research by exploring the effects of HGF/heparin-DLM patches on hepatocytes exposed to toxic treatments. Researchers used carbon tetrachloride (CCl4) to induce liver toxicity and tested two models: a prophylactic model, where healthy hepatocytes were pre-treated with the patches before exposure to toxins, and a therapeutic model, where previously damaged hepatocytes were treated with the patches to assess their recovery.

In their in vivo experiments with Sprague Dawley rats, they induced liver fibrosis using CCl4 over six weeks, then applied the HGF/heparin-DLM patches to the damaged liver for two weeks. Serum samples and liver tissue analysis showed that the patches could slow the progression of fibrosis and help restore liver function.

The development of cell-free hepatic patches represents a significant advancement in treating liver fibrosis and cirrhosis. By addressing the limitations of current cell-based therapies and leveraging the biocompatibility of DLM, these patches offer a promising new avenue for liver regeneration, aiming to provide effective treatments for patients suffering from severe liver diseases.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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