A FUTURISTIC treatment for diabetes has come a step closer with the discovery that liver tissue can be converted directly into tissue capable of making insulin. The work suggests it might one day be possible to turn part of a diabetic person’s liver into a replacement pancreas.
Much diabetes research focuses on turning unspecialised stem cells into the replacement tissues. But Jonathan Slack’s British-based team at the University of Bath is exploring a process called transdifferentiation: turning specialised adult cells directly into a different cell type.
The team modified frog embryos so that a gene called pdx1, normally active only in pancreatic cells, is switched on in liver cells as well. That turned the tadpoles’ liver cells into all cell types found in the pancreas, including insulin-producing islet cells. The tadpole cells were already becoming liver cells, says Slack, so it was not just a matter of altering the cells’ developmental pathway.
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The next step will be to try to convert part of the livers of adult diabetic mice into pancreatic cells to see if it cures them of the disease. There are hints that the method will work in people too: the team has managed to turn human liver cancer cells growing in culture into pancreatic-like cells.
Other scientists have achieved transdifferentiation by growing one cell type in a mashed-up soup of another. Philippe Collas at the University of Oslo in Norway is trying to create insulin-producing cells from skin cells by this method. He is excited by Slack’s results. “What I am most amazed about is that the conversion is long-lasting.” That gives him hope that the altered cells will continue to heed their new instructions when transplanted into the body.
Collas’s approach would avoid the need for gene therapy, under a cloud after two children in a French trial developed cancer. But skin would have to be taken from a patient’s body, converted into islet cells and then re-implanted. Slack’s approach could be as simple as injecting a gene therapy vector into a patient’s liver.
It is possible to get liver cells to make insulin simply by adding an extra insulin gene. The big challenge is controlling expression of the gene so that cells make just the right amount of insulin in response to changing blood sugar levels.
The hope is that islet cells created by transdifferentiation or from stem cells will be just as responsive to glucose levels as normal islet cells. However, people with juvenile diabetes might need repeated treatment, as the autoimmune attack that destroys their original islet cells would also destroy the new tissue.