A diabetes therapy with guts? Human gastric organoids engineered to produce insulin

Scientists inch closer to an autologous diabetes cell therapy that dodges the challenge of immune rejection, creating insulin-producing cells from the lining of the gut.

In a recent study, researchers from Harvard University (MA, USA), Peking University (Beijing, China), Jiangnan University (Wuxi, China), and Weill Cornell Medicine (NY, USA) genetically engineered human embryonic stem cells to create transplantable human gastric organoids that could be induced to release insulin – a feat that could prove transformative for type 1 diabetes treatment.

As of 2025, an estimated 9.5 million people worldwide are living with type 1 diabetes, in which beta cells are selectively destroyed by the immune system, and the pancreas, as a result, produces little or no insulin. One promising avenue for treatment involves transplanting insulin-secreting islets engineered from stem cells. However, this approach is hindered by donor scarcity and immune rejection, and as such must be accompanied by immunosuppression, which poses a number of potential health risks.

Using a patient’s own cells could bypass these hurdles. Previous research has demonstrated that insulin-secreting cells can be generated from mouse gut mucosa, but the same had never been achieved with human-derived cells in vivo before. This new research has changed that.

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The team engineered human embryonic stem cells to produce human gastric organoids composed of cells that could be induced to express three pancreatic reprogramming factors in the presence of doxycycline: NEUROG3, PDX1 and MAFA, collectively called NPM. The organoids, which resembled “mini-stomachs” in structure and cellular composition, were then transplanted into highly immunocompromised murine hosts.

After maturing for up to 6 months in the murine abdomen, the reprogramming factors were activated via the NPM “genetic switch”, which triggered the formation of pancreatic-like cells that produced insulin.

When the experiments were repeated in a mouse model of diabetes, the cells secreted human insulin into the bloodstream and ameliorated hyperglycemia, a hallmark of the metabolic condition.

“Our study provides proof of principle that human stomach tissue can be reprogrammed in vivo to produce functional insulin-secreting cells, laying the foundation for future development of an autologous, in situ therapeutic strategy for [type 1 diabetes],” the researchers conclude.

The researchers hope that insulin-producing cells could be induced in the human stomach using a patient’s own cells, avoiding issues of immune rejection. Although this is still a long way off coming to pass, and much more research is necessary to assess the safety and efficacy of such an approach, it is a promising step in the search for a functional cure for type 1 diabetes.