Induced insulin-producing cells derived from stomach tissue.
The researchers 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.
To find the body tissue most amenable to reprogramming for insulin production, the researchers genetically engineered mice to express three genes that can turn other cell types into beta cells.
They discovered that some of the cells in the pylorus (lower) region of the stomach are most amenable to conversion to beta cells. This tissue appears to be the best starting material.
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 normalize the mouse's blood sugar.
To test the cells' effectiveness, the researchers destroyed the pancreatic beta cells, forcing the mice to rely only on the altered stomach cells. Control animals, without tissue reprogramming, died within eight weeks. But the 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.
In various disease states there is a constant loss of beta cells. The discovery provides, in principle, an advantage to replenish those.
But to get closer to a potential therapy, the researchers had to take a different approach. When the mouse grew into an adult, the three genes were turned on. But in terms of a clinical future, "you can't do a transgenic human being," the researchers said.
So they 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 mini-organs were placed in the membrane that covers the inside of the abdominal cavity.
When the pancreatic cells were destroyed to see if the mini-organs would compensate, glucose levels stayed normal in five of the 22 experimental animals, which was the team's expected success rate.
The insulin-producing potential of the pyloric stomach cells likely comes from their natural similarity to pancreatic beta cells.
Many genes critical for beta cell function are also normally expressed in the pylorus's hormone-producing cells.
"What is potentially really great about this approach is that one can biopsy from an individual person, grow the cells in vitro and reprogram them to beta cells, and then transplant them to create a patient-specific therapy," co-author Qiao Zhou said.
Citation: Ariyachet et al., "Reprogrammed stomach tissue as a renewable source of functional beta -cells for blood glucose regulation," Cell Stem Cell, 2016 DOI: 10.1016/j.stem.2016.01.003
Contact: Qiao Zhou, firstname.lastname@example.org
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|Title Annotation:||Preclinical Research|
|Publication:||Stem Cell Research News|
|Date:||Feb 29, 2016|
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