Scientists Target Human Stomach Cells for Diabetes Therapy

Stem cells from the human stomach can be converted into cells that secrete insulin in response to rising blood sugar levels, offering a promising approach to treating diabetes, according to a preclinical study from researchers at Weill Cornell Medicine.

In the study, published in Nature Cell Biology, researchers at the Hartman Institute for Therapeutic Organ Regeneration showed that they could take stem cells obtained from human stomach tissue and reprogram them directly into cells that closely resemble pancreatic insulin-secreting beta cells. Transplants of small groups of these cells reversed signs of disease in a mouse model of diabetes.

“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 and severe type 2 diabetes,” said senior author Dr. Joe Zhou, who has been working on cell-based solutions for diabetes therapy for more than 15 years.

An estimated 1.6 million Americans have type 1 diabetes, which results from an autoimmune attack that destroys beta cells in the pancreas. An additional several million have severe type 2 diabetes.

Biomedical researchers aim to replace beta cell function in a more natural way, with transplants of human cells that work like beta cells: automatically sensing blood sugar levels and secreting insulin as needed. Ideally, transplants would use patients’ own cells to avoid the problem of transplant rejection.

In this new study, led by first author Dr. Xiaofeng Huang, researchers discovered that human gastric cells could be turned into insulin-producing beta cells by forcing the activation of three transcription factors or proteins that control gene expression, resulting in the subsequent activation of genes required for the development of normal beta cells.

When the team grew the cells in small clusters called organoids, they found that these organ-like pieces of tissue quickly became sensitive to glucose, responding with secretions of insulin. When transplanted into diabetic mice, the beta-like organoids suggested good durability and functioned largely as real pancreatic beta cells would, secreting insulin in response to rises in blood glucose, thereby keeping blood glucose levels steady.

Dr. Zhou said that he and his lab still need to optimize their method in various ways before it can be considered for clinical use.

Ultimately, the researchers hope to develop a technique enabling the relatively easy harvesting of gastric stem cells from patients, followed by the transplant of insulin-secreting organoids that regulate blood sugar levels without the need for further medication.

Illustration: Ollie Hirst