A team of researchers from Weill Cornell Medicine in the US has developed a novel way to treat diabetes using human stomach cells. They successfully transformed these cells into insulin-secreting cells that can reverse diabetes in mice. This breakthrough could pave the way for a potential cure for millions of people who rely on insulin injections to manage their condition.
Diabetes is a chronic disease that affects the body’s ability to regulate blood glucose levels. It occurs when the pancreas fails to produce enough insulin, a hormone that helps cells absorb glucose from the bloodstream. Insulin deficiency can lead to serious complications such as heart disease, kidney failure, blindness and amputation.
One of the main challenges in treating diabetes is finding a reliable source of insulin-producing cells that can replace the damaged or destroyed ones in the pancreas. Previous attempts have used stem cells from various sources, such as embryonic stem cells, induced pluripotent stem cells and adult tissue stem cells. However, these methods have faced limitations such as ethical issues, low efficiency, immune rejection and tumorigenicity.
The researchers from Weill Cornell Medicine decided to use gastric stem cells, which are abundant and easy to obtain from human stomach biopsies. These cells have the ability to regenerate the intestinal lining and differentiate into various gut-specific tissues. The researchers hypothesized that they could reprogram these cells into insulin-secreting cells by activating specific genes that control their fate.
To test their idea, they used a direct reprogramming approach based on the overexpression of three key transcription factors: Ngn3, Pdx1 and Mafa. These factors are known to play crucial roles in the development and function of pancreatic beta cells. By introducing these factors in a particular order, they were able to convert gastric stem cells into gastric insulin-secreting (GINS) cells within 10 days.
The GINS cells were then grown in small clusters called organoids and tested for their glucose responsiveness. The results showed that the GINS cells could sense and respond to changes in glucose levels by secreting insulin. Moreover, the GINS cells expressed genes that are characteristic of mature beta cells, such as Insulin, Pdx1, Mafa and G6pc2.
To evaluate the therapeutic potential of GINS cells, the researchers transplanted them into diabetic mice that lacked functional beta cells. They found that the GINS cell transplants were stable and effective for at least six months. They produced human insulin and reversed diabetes in mice without causing any adverse effects.
“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, an associate professor of regenerative medicine at Weill Cornell Medicine and senior author of the study.
The researchers hope that this approach could be used to treat people with diabetes using their own gut stem cells, limiting the risk of rejection. They also plan to optimize the reprogramming process and address the challenges of immune protection and long-term functionality of GINS cells.
“Gastric insulin-secreting (GINS) organoids exhibited glucose responsiveness 10\u2009days after induction,” the researchers wrote in their paper published in Nature Cell Biology. “They were stable upon transplantation for as long as we tracked them (6\u2009months), secreted human insulin and reversed diabetes in mice.”
This study represents a significant advance in the field of regenerative medicine for diabetes. It demonstrates the feasibility and efficacy of using stomach stem cells as a novel cell source for insulin replacement therapy. It also opens up new possibilities for exploring other types of cell conversions for treating various diseases.
Relevant articles:
– A guide from the stomach to β cells, Nature Cell Biology, 27 April 2023
– Stomach stem cells may be the key to curing type 1 diabetes, Interesting Engineering, May 2023
– Scientists Hacked Human Cells to Make Insulin, And It Reversed Diabetes in Mice, ScienceAlert, 03 June 2023
– Scientists reverse diabetes in mice by hacking human cells to make insulin, TechStartups.com, June 2023