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, which appeared April 27 in Nature Cell Biology, the researchers showed that they could take stem cells obtained from human stomach tissue and reprogram them directly — with strikingly high efficiency — into cells that closely resemble pancreatic insulin-secreting cells known as beta cells. Transplants of small groups of these cells reversed disease signs 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 diabetes and severe type 2 diabetes,” said study senior author Dr. Joe Zhou, a professor of regenerative medicine and a member of the Hartman Institute for Therapeutic Organ Regeneration at Weill Cornell Medicine.
Biomedical researchers aim to replace beta-cell function in a more natural way, with transplants of human cells that work as beta cells do: automatically sensing blood sugar levels and secreting insulin as needed.
Dr. Zhou has been working toward this goal for more than 15 years. In early experiments as a postdoctoral researcher, he discovered that ordinary pancreatic cells could be turned into insulin-producing beta-like 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. In a 2016 study, again in mice, he and his team showed that certain stem cells in the stomach, called gastric stem cells, are also highly sensitive to this three-factor activation method.
“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,” Dr. Zhou said.
After turning human gastric stem cells into beta-like cells, the team grew the cells in small clusters called organoids and 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 functioned largely as real pancreatic beta cells would, secreting insulin in response to rises in blood glucose, and thereby keeping blood glucose levels steady. The transplants also kept working for as long as the researchers monitored them — six months — suggesting good durability.
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, weeks later, of insulin-secreting organoids that regulate blood sugar levels without the need for further medication.
Xiaofeng Huang, Wei Gu, Jiaoyue Zhang, Ying Lan, Jonathan L. Colarusso, Sanlan Li, Christoph Pertl, Jiaqi Lu, Hyunkee Kim, Jian Zhu, David T. Breault, Jean Sévigny, Qiao Zhou. Stomach-derived human insulin-secreting organoids restore glucose homeostasis. Nature Cell Biology, 2023; 25 (5): 778 DOI: 10.1038/s41556-023-01130-y
Weill Cornell Medicine. (2023, May 25). Scientists target human stomach cells for diabetes therapy. ScienceDaily. Retrieved May 29, 2023 from www.sciencedaily.com/releases/2023/05/230525141422.htm
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