University of Geneva Announces Breakthrough in Diabetes Therapy: Reprogramming Pancreatic Cells to Secrete Insulin

VCBeat (WeChat Official Account: vcbeat) has learned that the University of Geneva (UNIGE) recently announced new progress in diabetes therapy.

It is well established that diabetes occurs when insulin-producing pancreatic beta cells are destroyed or become dysfunctional. The scientific community has long been dedicated to finding methods to regenerate these cells for the treatment of diabetes. Currently, researchers at the University of Geneva (UNIGE) have successfully converted other pancreatic cell types into insulin-secreting cells, demonstrating potential for a cure in mouse models of diabetes.

Five types of hormone-producing cells cluster in the pancreas to form what are known as pancreatic islets, and a Swiss research team reported in Nature that human α- and γ-endocrine cells within these islets can be reprogrammed to replace β-cells and produce insulin.

Kenichiro Furuyama, the first author of this research report, stated in a press release: “Simply aggregating cells with a single function stimulates the expression of genes associated with insulin secretion, as if ‘non-β’ cells can naturally detect their missing ‘sisters.’” However, these cells began to produce insulin only after researchers added proteins that regulate cell-specific gene transcription.

Pedro Herrera and his colleagues at the University of Geneva had previously demonstrated that mouse pancreatic cells can spontaneously change their identity to produce insulin. To test whether a similar mechanism exists in human cells, the scientists constructed pseudo-islets composed solely of one non-insulin-producing cell type. They found that increased expression of two key transcription factors, PDX1 and MafA, enabled α and γ cells to produce insulin.

The team reported that when these pseudo-islets were transplanted into mice lacking insulin-producing beta cells, the rodents recovered from type 1 diabetes, as their glucose tolerance and blood glucose levels returned to normal. Six months post-transplantation, the cells continued to secrete human insulin, with outcomes comparable to those observed with cells derived from both diabetic and non-diabetic donors.

Since type 1 diabetes is characterized by the autoimmune destruction of pancreatic beta cells responsible for insulin production, researchers sought to ensure that their modified cells would not become new targets of the immune system. Reassuringly, when these cells were co-cultured with T cells from patients with type 1 diabetes, they elicited a weak immune response. The researchers believe that these cells may be less susceptible to destruction than native beta cells.

Replacing missing or dysfunctional β-cells remains a prominent target for researchers seeking diabetes therapies. For instance, scientists at Stanford University have recently used zinc to guide a regenerative drug into β-cells; a research team at the University of Miami discovered that pancreatic stem cells can differentiate into β-cells; and leading biopharmaceutical giants AstraZeneca and Ionis are collaborating on antisense oligonucleotides designed to suppress genes associated with reduced insulin secretion.

Research findings from the University of Geneva provide early evidence of the ability of human pancreatic cells to alter their function under specific cellular conditions. “We must identify pharmacologically relevant approaches or gene therapies that can stimulate this change in cell identity within the patient’s own pancreas, without adversely affecting other cell types,” stated Pedro Herrera, noting that further work is required before translating this discovery into a therapeutic intervention.

(Compiled by Ning Chen)