Mini human livers grown from stem cells successfully implanted into rats
Imagine needing a liver transplant, and instead of waiting for a donor, a new one could be grown from your own skin cells. Scientists have now taken quite a big step towards that future, by successfully transplanting miniature human livers grown from induced pluripotent stem cells (IPSCs) into rats.
Organ transplants save lives, but there are hurdles to overcome. For one, there’s a constant shortage of donors and, even when one is found, the patient’s immune system often rejects the new tissue.
Growing a replacement organ from a patient’s own cells could solve both problems. It can be done on demand when a patient needs one, and the organ won’t be rejected because the immune system recognizes the cells as “self.”
In the new proof-of-concept study, researchers from the University of Pittsburgh grew livers from human cells and then transplanted them into rats. First, human skin cells are collected from volunteers. Then, these are reprogrammed into IPSCs, essentially returning them to a state where they can be differentiated into whatever types of cells are needed.
In this case, that’s liver cells. These human liver cells were then seeded into a rat liver that had had all its own cells stripped out. This leaves the scaffold behind for the new cells to stick to, retaining the original structure of the organ.
The researchers then transplanted these mini-human livers into five rats and monitored their condition for four days. In all cases, the new organs were working the whole time. They were secreting bile acids and urea, and the team detected human liver proteins in the rats’ blood serum.
That said, it didn’t go off completely without a hitch – blood flow problems developed around the grafts in all five rats. These animals had also been engineered to resist organ rejection, so the results may not have been as promising in other animals.
Still, it’s an exciting prospect. A similar procedure was performed a few years ago with mini hearts. These mini organs may one day grow up to become viable for human transplantation, and in the meantime they could be useful for testing drugs on more human-like organs within rats.
“The long-term goal is to create organs that can replace organ donation, but in the near future, I see this as a bridge to transplant,” says Alejandro Soto-Gutierrez, senior author of the study. “For instance, in acute liver failure, you might just need hepatic boost for a while instead of a whole new liver.”
Future work will need to focus on investigating long-term survivability, and other safety concerns.
The research was published in the journal Cell Reports.