Within a decade or so, the liver transplant waiting list will be a thing of the past.
Other organs will likely follow.
That’s the hope anyway, of some researchers.
New breakthroughs in a number of different research projects are speeding up the timeline until the day when a new liver can be grown in a lab and transplanted to a waiting patient.
Researchers expect to be able to do that by 2020.
While there are temporary fixes and drugs for patients waiting for a new heart or kidneys, patients in need of a new liver typically get sicker and sicker until they die, unless a donated organ comes in time.
More than 7,800 livers were transplanted into such patients in 2016.
But more than 14,000 Americans are currently on the waiting list.
The most common reasons for the transplants are chronic hepatitis C, followed by complications from long-term alcohol abuse, other forms of hepatitis, various genetic conditions diseases in the bile ducts, or cancers originating in the liver.
If successful, the various efforts to grow livers in the lab could mark a turning a point for these desperate patients.
Growing liver ‘micro-buds’
In one project, researchers they have overcome previous hurdles and are able to bioengineer batches of 20,000 liver “micro-buds.”
When combined, the buds are large enough for transplant.
That project is led by the Cincinnati Children’s Center for Stem Cell and Organoid Medicine and Japan’s Yokohama City University.
It has focused on trying to grow the new livers from a patient’s own stem cells, eliminating the risk of the body rejecting the new organ.
Previous methods have relied on bone marrow and cells from umbilical cords to grow new liver cells, but those sources are more difficult and controversial to obtain.
Now, said lead investigator Takanori Takebe, “we can generate mini buds entirely from stem cells (and) we can generate mini buds in much larger scale for patient applications.”
Takebe’s team grew the liver tissues in custom-designed cell plates with U-shaped bottoms.
That helped them avoid using animal-derived products to help grow the new livers.
The technique should help them meet clinical manufacturing standards, Takebe said.
Using animal livers
Another project is using animal products, but stripped of any cells, in a way that should also meet clinical-grade standards.
Jeff Ross’ starts with pig livers, leftover from pork butchering, and decellularizes them.
“We remove all the cellular material from the liver, but the architecture is still there. We have a perfect architecture of the organ,” Ross, the chief executive officer of Minnesota-based Miromatrix Medical, told Healthline.
Having that scaffolding, or functional vasculature, overcomes what he says has been one of the major roadblocks in being able to engineer livers in the lab.
Without it, achieving continuous blood flow through the manufactured organ without clotting can be tricky.
The ghostly white former pig liver is then recellularized with liver cells.
Those are currently derived from donated livers that weren’t viable for transplant for various reasons.
In the future, Ross hopes they can derive the livers from stem cells so that each liver would be individualized for the patient, eliminating the need for immunosuppressives.
“Our whole goal is to eliminate the organ transplant list by creating bioengineered organs,” Ross said. “And our long-term goal is creating them from patients’ own cells to eliminate rejection.”
Human transplants could start in 2020
By the middle of 2018, Ross hopes they will be able to transplant a recellularized liver back into a pig and show it has complete functionality.
By 2020, he hopes to transplant the first such livers in human patients in a phase 1 clinical trial.
Those livers, he said, “should last years, if not forever.”
Takebe’s team also hopes to begin transplanting their bioengineered livers in human patients in clinical trials in 2020.
The use of fetal stem cells in research has come under fire in other areas, but since Takebe is working with patients’ own stem cells, he said he doesn’t anticipate any ethical concerns.
Ross’ use of organs harvested from animals may raise some eyebrows, but the organs are typically discarded anyway in the butchering.
And, Takebe added, any ethical concerns would need to be weighed against the harm or deaths involving those waiting on the organ transplant list.
“Given that many patients are dying from end-stage conditions, they are in critical need for transplant,” he said.