While the exact cause of type 1 diabetes is not known, it is believed to be caused by an autoimmune response in which the body attacks and destroys the beta cells in the pancreas, the cells that produce insulin. For years, researchers have looked at a “cure” for diabetes using stem cells to create insulin-producing cells to replace those destroyed by the immune system.
Stem cells in the human intestine, gastric stem cells, perform the remarkable feat of regenerating our intestinal lining every five to seven days. They also differentiate into specific gut tissues, including enteroendocrine cells (EECs), which secrete hormones. Being able to generate EECs that secrete the hormone insulin would be of great therapeutic value for type 1 diabetics whose beta cells have stopped producing or do not produce enough insulin.
Now, researchers at Weill Cornell Medicine have achieved this by converting human gastric stem cells into insulin-secreting cells that respond to blood glucose levels in the same way as healthy pancreatic beta cells.
“The stomach produces its own hormone-secreting cells, and stomach cells and pancreatic cells are adjacent in the embryonic stage of development, so in that sense it is not entirely surprising that gastric stem cells can be so readily turned into insulin. beta type. -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 that he could convert common 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 an endoscopy, in which a thin, flexible tube with a camera (an endoscope) is inserted through the mouth into the stomach. The endoscope is equipped with a tool that allows the operator to take tissue samples.
After converting gastric stem cells into beta-like cells called gastric insulin-secreting cells (GINS). The researchers turned them into tiny clumps called organoids, which they say became glucose sensitive within 10 days and responded by secreting insulin.
When GINS were transplanted into diabetic mice, they behaved like real pancreatic beta cells, responding to increases in blood glucose by secreting insulin to keep blood glucose levels stable. The transplanted cells continued to produce insulin for as long as the researchers monitored them, six months. This, they say, indicates its sturdiness.
“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,” said Zhou.
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, either 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 transplanting insulin-secreting cells created from a patient’s stem cells is a more natural way to improve beta cell function and would reduce the problem of transplant rejection.
The researchers will optimize their method before moving on to clinical trials, including scaling up the production of beta-like cells for human transplantation. Importantly, they are 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