Researchers have taken stem cells from the human stomach and converted them into insulin-producing cells that respond to changes in blood glucose levels like healthy pancreatic cells would. The discovery could mean that one day, diabetics can produce their own insulin instead of relying on injections.
Although the exact cause of type 1 diabetes isn’t known, it’s thought to be caused by an autoimmune response where the body attacks and destroys the pancreas’ beta cells, the cells that produce insulin. For years, researchers have looked at ‘curing’ diabetes by using stem cells to create insulin-producing cells to replace the ones destroyed by the immune system.
Stem cells in the human gut, gastric stem cells, perform the remarkable feat of regenerating our intestinal lining every five to seven days. They also differentiate into gut-specific tissues, including enteroendocrine cells (EECs), which secrete hormones. Being able to generate EECs that secrete the hormone insulin would be of great therapeutic value to type 1 diabetics whose beta cells have stopped producing, or don’t produce enough, insulin.
Now, researchers from Weill Cornell Medicine have achieved that, converting human gastric stem cells into insulin-secreting cells that respond to blood glucose levels just as healthy pancreatic beta cells would.
“The stomach makes its own hormone-secreting cells, and stomach cells and pancreatic cells are adjacent in the embryonic stage of development, so in that sense it isn’t completely surprising that gastric stem cells can be so readily transformed into beta-like insulin-secreting cells,” said Joe Zhou, corresponding author of the study.
It’s a goal Zhou has been working towards for more than 15 years. Through early experiments, he discovered he could convert ordinary pancreatic cells in mice into insulin-secreting beta cells by forcing the activation of three transcription factors, proteins that control gene expression. In 2016, again using mice, he and his research team found that gastric stem cells are also highly sensitive to this three-factor activation method.
In the current study, the researchers removed the gastric stem cells through a simple non-surgical procedure called endoscopy, where a thin, flexible tube with a camera on it (an endoscope) is inserted through the mouth into the stomach. The endoscope is fitted with a tool that allows the operator to take tissue samples.
After converting gastric stem cells to beta-like cells called gastric insulin-secreting cells (GINS). The researchers grew them into small clusters called organoids, which, they found, became sensitive to glucose within 10 days and responded by secreting insulin.
When the GINS were transplanted into diabetic mice, they behaved much like real pancreatic beta cells would, responding to rises in blood glucose by secreting insulin to keep blood glucose levels steady. The transplanted cells continued to produce insulin for the time the researchers monitored them, six months. This, they say, indicates their robustness.
“This is a proof-of-concept study that gives us a solid foundation for developing a treatment, based on patients’ own cells, for type 1 diabetes and severe type 2 diabetes,” Zhou said.
Worldwide, there were an estimated 8.4 million people living with type 1 diabetes in 2021. By 2040, this number is expected to rise to between 13.5 million and 17.4 million. Currently, type 1 diabetics treat their condition with insulin, injected manually or continuously using a wearable insulin pump. Some people with advanced type 2 diabetes need to take insulin to supplement their body’s insufficient levels.
The researchers say that transplanting insulin-secreting cells created from a patient's stem cells is a more natural way of improving beta cell function and would reduce the problem of transplant rejection.
The researchers will optimize their method before advancing to clinical trials, including increasing the scale of beta-like cell production for transplantation in humans. Importantly, they’re working on modifying the cells to make them less susceptible to the immune system attack that destroys beta cells in type 1 diabetics.
The study was published in the journal Nature Cell Biology.
Source: Weill Cornell Medicine
