Scientists have successfully developed 'mini-organs' that produced insulin when transplanted into the mice, an advance that could lead to patient-specific therapy for diabetics.
Researchers have spent decades trying to replace the insulin-producing pancreatic cells, called beta cells, that are lost in diabetes. Scientists, including those from Harvard University, have discovered that tissue from the lower stomach has the greatest potential to be reprogrammed into a beta-cell state. They took samples of this tissue from mice and grew them into "mini-organs" that produced insulin when transplanted back into the animals.
The mini-organs' stem cells also continued to replenish the insulin-producing cell population, giving the tissue a sustainable regenerative boost. "We discovered, surprisingly, that some of the cells in the pylorus region of the stomach are most amenable to conversion to beta cells. This tissue appears to be the best starting material," said Qiao Zhou, of the Harvard University.
The pylorus region connects the stomach to the small intestine. When reprogrammed, cells in this area were the most responsive to high glucose levels, producing insulin to normalise the mouse's blood sugar. To test the cells' effectiveness, the researchers destroyed the mice's pancreatic beta cells, forcing their bodies to rely only on the altered stomach cells.
Control animals, without tissue reprogramming, died within eight weeks. However, the experimental mice's reprogrammed cells maintained insulin and glucose levels in their blood for as long as the animals were tracked, up to six months. The pyloric stomach has another advantage - stem cells naturally renew the gut tissue on a regular basis.
When cells in the pyloric stomach expressed the conversion genes, and the first set of reprogrammed cells were experimentally destroyed, the region's stem cells refreshed the insulin-producing cell population. "When the mouse grew into an adult, we turned on the three genes. But in terms of a clinical future, you can't do a transgenic human being," he said.
Researchers took stomach tissue from the mice, engineered it to express the beta-cell reprogramming factors in the lab, and coaxed the cells to grow into a tiny ball of a mini-stomach that would both produce insulin and refresh itself with stem cells.
The team then placed these mini-organs in the membrane that covers the inside of the mouse's abdominal cavity. When the researchers destroyed the mice's pancreatic cells to see if the mini-organs would compensate, they found that glucose levels stayed normal in five of the 22 experimental animals, which was the team's expected success rate.
"What is potentially really great about this approach is that one can biopsy from an individual person, grow the cells in vitro and reprogramme them to beta cells, and then transplant them to create a patient-specific therapy," Zhou said.
The study was published in the journal Cell Stem Cell.
