The future for artificial livers
Chinese researchers have built an artificial liver that supports a patient's own failing liver and helps it to repair itself...
So how you achieve something like this? The biological component of this device is the key to its success. The scientists generated renewable human liver cells to build a working artificial liver. By carefully tweaking genes in mature cells, they reprogrammed the cells, unspecialising them and producing rapidly-dividing liver stem cells. These were then grown as 3d spherical clumps of cells and loaded into an artificial liver device. The resulting system was then tested in pigs with liver damage. Animals given the artificial liver treatment had significantly less tissue damage and showed improved regeneration of their own livers after a drug-induced injury, resembling a drug overdose in humans, to their own livers. Although it's early days, the ultimate aim is, one day, to use this in humans who desperately need a working liver.
But how do you turn old cells into rapidly-growing stem cells? This requires a fine-tuned approach. To genetically modify human liver cells to endow them with the capacity to grow and produce billions of functional new ones, it is critical to choose the correct gene or genes to reprogramme the cells so they turn back into stem cells. Targeting the wrong gene creates liver tissue that loses some of the key liver functions over time. Deployed clinically, this would render the device unsafe and ineffective.
Was the creation of liver tissue performed in a specific manner? Yes, it was important to build 3 dimensional spheres to produce tissue that performed best. The liver spheres were grown in the artificial device, prior to treating liver failure in pigs. The device was termed an air-liquid interactive bioartificial liver and provided the growing liver cells with oyxgen and nutrition, protection from biochemical stress, and promoted the direct interaction of the pig blood plasma with the liver spheres, enabling them to clean and detoxify the blood more efficiently.
How did the researchers test the artificial liver device? The safety and efficacy of the device was evaluated in pigs with liver failure. Following treatment, the control experimental group of animals, which received critical care only, had a 20% survival rate. In sharp contrast, the survival rate among animals supported by the artificial liver device was 80%, showing boosted liver function and improved waste product removal.
Was aided liver function and improved survival rates the only outcomes of this research? No, excitingly the study demonstrated that the device also promoted organ regeneration following treatment. The authors suggested that the healing factors produced and secreted by the artificial liver may have kickstarted organ regeneration in the host.
Scaling up the technology to levels that would be useful for a clinical trial are notoriously challenging, so what are the chances that this technology could make it to the clinic? Notably the device was quick to manufacture (within 2 weeks) and demonstrated good batch-to-batch consistency. This is a strong starting point, with both attributes essential for clinical grade manufacture to test the safety and efficacy of the device in human trials.
Working in the field myself, I think these studies offer an exciting prospect to treat human liver disease in the future. Of particular note, are the author’s ability to improve clinical outcome and tissue regeneration after only three hours of artificial liver treatment. These results suggest that the device may be an exciting candidate treatment for failing liver function in humans. I am excited to see how this technology develops, and if the authors can address the manufacturing challenges to move this technology toward human clinical trials in the near future.