Big liver news! Two discoveries released yesterday point towards a future without the need for liver transplants.
Liver cells are famous for their ability to proliferate in the body (slice out two-thirds and the remaining third will quickly regenerate a normal organ). But end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy its regenerative ability.
A new study shows how cells taken from the tips of mouse tails and genetically reprogrammed to mimic mature liver cells can repair damaged livers. The same technique could ultimately be used to reprogram human cells and reduce the need for transplants. Nature News reports.
Liver cells have always posed a problem for cellular reprogrammers because of their many, many functions – from breaking down toxins to producing proteins.
Lijian Hui of the Shanghai Institute for Biological Sciences and his team tackled this problem by sifting through 14 proteins known to be important for activating genes in liver cells.
- First they persuaded fibroblasts (cells found in connective tissue) from mouse tails to behave like liver cells.
- Then they transplanted those engineered cells into mice who lacked a gene for detoxifying certain compounds (so they’re sort of like mice with liver injuries).
- Mice who didn’t receive the transplants died, but 5 of the 12 mice who received the engineered cells survived, thanks to restored liver function.
This is the first time that reprogrammed cells – that are produced without passing through a stem cell stage – have fixed a damaged organ. The process is called transdifferentiation.
They show how human cells reprogrammed in this way repaired damaged mouse livers just as well as normal human liver cells.
- First, adult skin or blood cells were converted into a type of stem cell called an induced pluripotent stem cell (iPSC).
- Those cells were chemically coaxed into behaving like liver cells, and then injected into mice with cirrhosis.
- The human iPSC-derived liver cells grew into fresh mouse liver tissue with 8 to 15% efficiency. (With adult human liver cells, that rate is about 11%.)
These iPSCs can be generated from a tiny amount of a patient’s own tissues and grown indefinitely in a dish. That way, large amounts of liver cells can be tailored to each patient, preventing the immune-rejection problems that come with unmatched donors.
The next steps for both studies will be to translate the work to humans, which will be huge for tissue engineering and regenerative medicine.
Image: liver samples / Yoon-Young Jang