A DRI discovery paves the way for a pharmacological approach which could help the pancreas heal itself.
MIAMI, FL (October 27, 2023) – A groundbreaking technique has been established which has allowed scientists from the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine to culture live sections of the pancreas for nearly two weeks. The scientists have used the living pancreas sections to chart the first dynamic single-cell map of the regenerative pathways of the pancreas. The results, published recently in the prestigious journal Cell Metabolism, indicate that a secreted growth factor can cause pancreatic stem-like cells to move from the ducts where they reside and to change into insulin-producing cells (pancreatic islet beta cells).
The pancreatic slices are thin living sections in which the cellular architecture and cell-to-cell interactions of the original pancreas are preserved. Scientists from the DRI had previously fashioned the conditions needed for long-term culture, but this study goes one step further by applying a technology called single-cell RNA sequencing (scRNAseq) that allows for the sequencing of thousands of genes within the slice. Sequencing slices at different time points in the presence or absence of factors such as the growth factor BMP-7, led to the first-ever dynamic analysis of pancreatic regeneration.
Juan Dominguez-Bendala, Ph.D. (at the microscope), and Ricardo Pastori, Ph.D., found that BMP signaling remained intact for patients with type 1 diabetes.
“This analysis takes the shape of single-cell maps where different cell types are grouped into continents and countries”, said Dr. Juan Domínguez-Bendala, PhD, Professor of Surgery, Director of the Pancreatic Regeneration and Stem Cell laboratory, and principal investigator of this work. “scRNAseq analyses had previously suggested that progenitors may be able to become insulin-producing cells, but it was nothing more than a prediction. Looking at how single-cell maps of pancreatic slices from the same donor evolve with time, with or without BMP-7, confirmed that progenitor cells do leave their country and ‘migrate across the ocean’ to regenerate into islet beta cells elsewhere.”
The pancreas has a surprising repertoire of mechanisms that can replenish damaged cells. The DRI research suggests that BMP-7 is able to work on the reactivation of the very program that gave rise to the pancreas during embryonic development. However, the DRI investigators wanted to know more: “Is this mechanism disabled in patients with T1D?”, asked Ricardo Pastori, Ph.D., Professor of Medicine, Immunology, and Microbiology, Director of the Molecular Biology Laboratory, and co-principal investigator of this study. To investigate this, the Network of Pancreatic Organ Donors with Diabetes (nPOD) sent the DRI team some of their most precious samples: live pancreatic slices from donors with T1D. Using a novel strategy, they showed that BMP-7-like molecules were able to induce the formation of new beta cells that were able to secrete insulin in response to glucose stimulation. “This is the true measure of beta cell functionality, and our results confirm that the regeneration pathways activated by BMP signaling remain intact in patients with T1D”, concluded Dr. Pastori.
As demonstrated by DRI investigators with dynamic single-cell analyses of cultured pancreatic slices from donors with T1D, the ductal tree (green cells) contains pancreatic progenitors with the ability to create new insulin-producing cells (red cells).
“We have cured diabetes in dozens of different ways in preclinical models and none has worked in humans so far, so it is understandable that some people may be desensitized to the impact of some of these advances”, added Dr. Domínguez-Bendala. “But to bring back the beta cells in a real, live piece of the pancreas from a donor with T1D? It doesn’t get much more promising than that”
These findings will be the basis for the development of pharmacological interventions to harness and accelerate the natural ability of the pancreas to restore its own beta cells, bringing new hope to millions of patients with T1D.
About the DRI
The DRI at the University of Miami Miller School of Medicine leads the world in cure-focused research. As one of the largest and most comprehensive research centers dedicated to curing diabetes, the DRI is aggressively working to develop a biological cure by restoring natural insulin production and normalizing blood sugar levels without imposing other risks. Researchers have already shown that transplanted islet cells allow patients to live without the need for insulin therapy. Some study participants have maintained insulin independence for more than 10 years. For more information, please visit DiabetesResearch.org, call 800-321-3437, or Tweet @Diabetes_DRI.