It sounds like a scene from a sci-fi movie: Scientists create a weapon that neutralizes a bad invading entity and maybe even turns it into a force for good. That's a bit like what researchers at the University of California San Francisco (UCSF) have just done. Only in this case, the invaders are disease-causing liver cells and the "weapon" involves a bit more than special effects.
Because grafting organs is still a challenging procedure and the waiting list for organ transplants can be long, the UCSF researchers turned to another strategy particularly designed to help patients suffering from liver fibrosis, a condition brought on when healthy liver cells called hepatocytes can't regenerate fast enough to keep up with damage being caused by toxins like alcohol or by diseases like hepatitis C. When that happens, cells called myofibroblasts fill in the gaps left when hepatocytes die and cause a build-up of fibrous tissue in the liver that impair its function.
Livers filled with this fibrous tissue are especially resistant to grafts of transplanted cells that could help the organ regenerate itself. So instead, the UCSF method uses a virus to deliver a batch of gene-regulating proteins to the myofibroblasts that cause them to flip back into healthy hepatocytes. The virus is known to specifically infect myofibroblasts, so it serves as a particularly effective delivery system — kind of like a virus delivery truck.
The method, in effect, heals the liver from the inside out.
In tests of the technique, the research team showed that less than one percent of myofibroblasts in an infected mouse were converted into healthy cells. While that doesn't sound like a large amount, sometimes that's all that's needed to improve liver function. In fact, a liver can operate with up to 80 percent of its makeup taken over by myofibroblasts – when the fibrous tissues increases beyond that though, trouble ensues. So the new technique could beat back the damaging tissue to acceptable levels and extend patients' lives.
The team, led by UCSF professor of surgery, Holger Willenbring, also demonstrated an effective use of the technique in human liver cells in a dish but say more work is necessary before human trials would be possible.
Once the research gets to that level, it will likely act as more of a temporary bridge than a cure for liver disease, says Willenbring. "A liver transplant is still the best cure," he states. "This is more of a patch. But if it can boost liver function by just a couple percent, that can hopefully keep patients' liver function over that critical threshold, and that could translate to decades more of life."
The research is detailed in a paper published June 2 in the journal Cell Stem Cell.
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