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September 01, 2017

One more step to making pancreas in the lab

The Kenji Osafune Lab reports AT7867 promotes the proliferation of pancreatic progenitor cells.

Immune cells are the body's military, fighting off invading pathogens. Sometimes, these soldiers will mutiny and kill their own. Such is the case in type 1 diabetes, where the immune system destroys pancreatic islet cells, the cells responsible for producing insulin. Some patients can be managed with insulin injection, but only islet or whole pancreas transplantations have been shown to cure the disease.

Because of the shortage of donors, scientists have been searching for ways to prepare islet cells in the lab. CiRA researchers have discovered that AT7867, a drug compound known to have anti-cancer therapeutic potential, can enhance the production of pancreatic progenitors cells.

Pancreatic progenitor cells produce all cells in the pancreas. CiRA Professor Kenji Osafune and Junior Associate Professor Taro Toyoda have proposed using iPS cells to prepare and store pancreatic progenitor cells that can then be made into islet cells.

"It is difficult to store islet cells for a long time. We can store iPS cells and pancreatic progenitor cells, but pancreatic progenitor cells are advantageous because they shorten the handling period," they said.

The two led a team of scientists who searched databases and conducted chemical screenings to find drug compounds that enhanced the production of pancreatic progenitor cells from iPS cells.

The study shows that adding AT7867 to standard differentiation protocols enhances pancreatic progenitor cell levels. AT7687 inhibits AKT phosphorylation to give it an anti-cancer effect. But the molecular effect that enhances pancreatic progenitor cell proliferation is for future study.

While the pancreatic progenitor cells themselves do not produce insulin, they could be differentiated into islet cells that do with further manipulation.

The cells are expected to be useful for drug discovery and drug toxicity studies as well as cell therapy against diabetes.

Paper Details
  • Journal: Stem Cell Research
  • Title: Small molecule AT7867 proliferates PDX1-expressing pancreatic progenitor cells derived from human pluripotent stem cells
  • Authors: Azuma Kimura, Taro Toyoda, Yohei Nishi, Makoto Nasu, Akira Ohta and Kenji Osafune
  • Author Affiliations:
    Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
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