When James Luyendyk and his team at Michigan State University set out to study how the liver repairs itself after surgery, they expected to confirm what earlier research had suggested. Instead, they discovered something that turned their hypothesis on its head — and it could eventually help prevent one of the most dangerous complications of liver surgery.
The liver is one of the body's most remarkable organs: unlike most tissues, it can regrow after significant damage, making life-saving procedures possible for thousands of patients each year. But not every patient recovers as expected. Post-hepatectomy liver failure — when the remaining liver struggles to regenerate — remains a leading cause of death after liver surgery. Understanding why some patients falter while others recover has been a puzzle researchers have long tried to solve.
Luyendyk, who holds the Albert C. and Lois E. Dehn Endowed Chair in Veterinary Medicine at Michigan State University's College of Veterinary Medicine, studies the intersection of blood clotting and liver biology. His team focused on plasminogen, a protein involved in breaking down blood clots that prior research had suggested played an important role in regeneration. The intuitive assumption was clear: more plasminogen would support the process. The data said otherwise.
When researchers reduced plasminogen levels in mice, the animals' livers produced more new cells and showed stronger signs of regeneration after surgery. The result was essentially the opposite of what the team had anticipated. "Science moves forward when you're willing to follow the data, even when it tells you you're wrong," Luyendyk said. "In this case, the data challenged what we thought we knew about liver regeneration and opened an entirely new path for investigation."
The findings, published in the journal Blood, caught the attention of Patrick Starlinger, a liver surgeon and researcher at the Mayo Clinic. Starlinger was already involved in a multicenter clinical trial called HeLiX, evaluating tranexamic acid — a widely used medication that reduces bleeding during surgery. Inspired by the Michigan State findings, his team examined whether the drug's effects on the plasminogen pathway might also influence how patients' livers recovered.
The results were striking. Patients who received tranexamic acid had roughly three times lower odds of developing post-hepatectomy liver failure compared to those who received a placebo. "The possibility that a widely available, low-cost medication could substantially reduce this risk is exciting," Starlinger said. "It has the potential to improve outcomes for patients undergoing surgery for liver cancer and other serious liver diseases."
The research also illustrates the power of what the scientific community calls One Health — an approach that recognizes the connections between human, animal, and environmental health. What began in a veterinary medicine laboratory in Michigan eventually helped shape a clinical investigation involving human patients. "This is exactly the kind of cross-species learning that One Health is all about," Luyendyk said. "We learn something in a setting, test it in another, and use those insights to improve health across species."
While further studies are needed before tranexamic acid could become standard practice for protecting liver regeneration, the findings point to a promising new direction — and a reminder that sometimes the most important discoveries come from following the data where it leads, not where we expect.