From the pages of Mayo Clinic Magazine.
The spheroid liver cell (hepatocyte). Millions of these are needed to approximate the function of the natural human liver.
A few years ago, nature dealt a fatal blow to Cassandra Rohrer, a 16-year-old patient of Scott Nyberg, M.D., Ph.D. She was fighting for her life with the assistance of an experimental artificial liver device, which was keeping her alive but couldn’t do so much longer. She needed a liver transplant.
After two days on the device, her family got the news that an organ was available and being flown from Michigan. The family and a team of caregivers jumped into action, preparing the girl for her lifesaving transplant. But the team delivering the liver got caught in a thunderstorm and didn’t make it in time. The girl became neurologically unstable and did not wake up after surgery.
“People with liver failure, one of the main causes of death is ammonia buildup in your blood,” Dr. Nyberg says. “Proteins break down and produce ammonia, essentially making oven cleaner, and it causes your brain to swell and you die from brain herniation. If any one of us overdoses from Tylenol and kills our liver, we’d die of brain herniation probably in two to three days if we didn’t get a liver transplant.”
Since then, Dr. Nyberg has kept a picture of Cassandra to remind him why he spends long hours searching for new treatments.
His search has taken him to places unimaginable 10 years ago. He began his work seeking to build a better artificial liver device, one that uses large doses of human liver cells and can treat patients for longer periods of time until they receive a transplant. It’s still a primary goal, but now he envisions also using a patient’s stem cells to bioengineer healthy liver cells, then transplanting them back to the patient to cure a diseased liver.
“Doctors are already doing liver cell transplants, but the supply of human cells is very limited, so there are only a few of them done a year,” Dr. Nyberg says. “Many diseases you can treat and cure with just the cells. There’s a large demand for cell transplants.”
He and colleagues in Mayo Clinic’s Center for Regenerative Medicine are pioneering a method to grow a large number of patient-specific liver cells to meet demand. They are also using these cells to try to create whole new livers, tailored to individual patients.
Today, there are simply not enough livers available. About one in ten people on the liver transplant waiting list will die before an organ becomes available.
A contributing factor to the shortage is that sometimes a donated liver has a defect that makes it unusable. To save more lives, Dr. Nyberg is working with the regenerative medicine company Miromatrix to remove all the cells from these defective livers, leaving only a scaffold. He’s working with Mayo Clinic’s Allan Dietz, Ph.D., to populate the scaffold with stem cells taken from the patient, creating a whole new organ.
This tailor-made liver accomplishes two goals: It overcomes the hurdle of immunosuppressant medicines, and it makes more livers available.
A traditional organ transplant introduces foreign tissue into the body, which triggers the patient’s immune system to attack the new organ. To suppress the response, transplant patients take a cocktail of medicines for the rest of their lives. These medications are expensive and can have serious side effects. However, a liver built with the patient’s cells would end the need for immunosuppressants.
It would also help ensure that patients like Cassandra would have a liver when they needed one.
Read more about liver regeneration at Mayo Clinic.
Read more about Mayo Clinic's bioartificial liver in Discovery's Edge, Mayo's research magazine.
Tags: liver regeneration, liver transplant, Mayo Clinic, regenerative medicine, Research, scott nyberg