Researchers say they have reversed equivalent of type 1 diabetes in mice using stem cell transplants
Scientists believe they may have moved a step closer to a cure for the type of diabetes that develops in childhood and usually leads to a lifetime of insulin injections.
Researchers in California report that they have reversed the equivalent of type 1 diabetes in mice through transplants of stem cells. Their experiments have replaced cells in the pancreas damaged by the disease that are unable to make insulin.
Without insulin, the body has difficulty absorbing sugars such as glucose from the blood. The disease usually first shows in childhood or early adulthood and used to be a killer, but glucose levels can now be monitored and regulated with insulin injections.
Scientists have long wanted to try to replace the damaged ß-cells that normally produce insulin. This has been one of the prime targets of stem cell experiments. But until now, it has proved difficult, partly because mature ß-cells do not readily regenerate.
Writing in the journal Cell Stem Cell, scientists at the Gladstone Institutes in San Francisco describe how they took a step back and collected skin cells, called fibroblasts, from laboratory mice. Then, by treating the fibroblasts with a unique "cocktail" of molecules and reprogramming factors, they transformed the cells into endoderm-like cells. Endoderm cells are a type of cell found in the early embryo, and which eventually mature into the body's major organs – including the pancreas. "Using another chemical cocktail, we then transformed these endoderm-like cells into cells that mimicked early pancreas-like cells, which we called PPLCs," said the Gladstone postdoctoral scholar Ke Li, the paper's lead author. "Our initial goal was to see whether we could coax these PPLCs to mature into cells that, like ß-cells, respond to the correct chemical signals and – most importantly – secrete insulin. And our initial experiments, performed in a petri dish, revealed that they did."
The team then injected these cells into mice that had been genetically modified to have high glucose levels, mimicking the type 1 diabetes condition in humans.
"Importantly, just one week post-transplant, the animals' glucose levels started to decrease, gradually approaching normal levels," said Li. "And when we removed the transplanted cells, we saw an immediate glucose spike, revealing a direct link between the transplantation of the PPLCs and reduced hyperglycemia [high glucose level]."
Eight weeks after the transplantation, the scientists found that the pancreas-like cells had turned into the real thing – fully functional insulin-secreting ß-cells had developed in the mice.
The team says this is proof of principle, which one day might be used to cure type 1 diabetes in humans. "I am particularly excited about the prospect of translating these findings to the human system," said Matthias Hebrok, one of the study's authors and director of the UCSF Diabetes Center. "Most immediately, this technology in human cells could significantly advance our understanding of how inherent defects in ß-cells result in diabetes, bringing us notably closer to a much-needed cure."
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