New mathematical model promises to improve production of insulin-producing cells

Patients suffering from type 1 diabetes will be indirectly helped by a new mathematical model developed by researchers at reNEW and the Niels Bohr Institute at the University of Copenhagen. The developed formulas provide insight on how cells specialize. This knowledge will help researchers to improve the methods used to cultivate pancreatic beta cells from stem cells. The aim is to transplant such cells into diabetics who lack properly functioning insulin-producing cells.

As the fetus develops during pregnancy, cells specialize into different cell types. The very first decision triggering cell differentiation in the pancreas is activated by signaling molecules (Jag1-Notch) found in fetal pancreas cells. “We had an idea of how this (signaling) process worked thanks to observations with mouse genetics but could not prove it conclusively with (traditional) mouse models. This is why our breakthrough, a new mathematical model, matters,” says Professor Palle Serup, who is a leading researcher in pancreatic development at reNEW.

Stem cell-derived, insulin-producing beta cells stained by immunofluorescence for insulin (red) and Pdx1 (green). Photo: Assistant Professor Philip Allan Seymour.

A group of physicists* at the Niels Bohr Institute teamed up with the Serup lab at reNEW to develop the groundbreaking model composed of five mathematical equations. They ran countless simulations to show the equations’ ability to accurately model pancreas development in 3D. “Thanks to the models, we can now perform ‘what if’ experiments on a computer and pinpoint different scenarios where the signaling molecule is needed,” Serup explains. The goal of Serup and his team is to improve the efficiency of the production of insulin-producing pancreatic beta cells from stem cells thanks to these experiments.

This matters for patients suffering from type 1 diabetes, a genetic and chronic condition that typically shows up in early life. The disease requires daily and multiple insulin injections for life. In 2021, around 10 million people worldwide were diagnosed with type 1 diabetes and their number is growing. By 2040, this figure is expected to have nearly doubled, according to data published in the Lancet Diabetes Endocrinol.

To date, the methods used to cultivate pancreatic cells from stem cells are inefficient and costly. It takes about a week for a stem cell to differentiate into an early pancreas cell, but another three weeks to reach insulin-producing pancreatic cells in the lab. The end result is not optimal, as these cultivated cells often are not pure enough. “Our mathematical model provides a basis for experiments aimed at improving this process which in turn could slash the cost of producing insulin-producing pancreatic cells,” Serup says. Pancreatic cells available for transplantation into the pancreas of diabetics would as a result be more readily available, at lower cost.

The ongoing interdisciplinary collaboration between reNEW and the Niels Bohr institute will continue over the coming years, to refine the mathematical model just described. “The developed mathematical framework focuses on the development of pancreatic beta cells but can be applied to any other cell types,” Dr. Xiaochan Xu from the Niels Bohr Institute concludes.

Additional information can be found in the article “Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development,” published in nature communications.

* Dr. Xiaochan Xu, Professors Mogens Høgh Jensen and Kim Sneppen, and Associate Professor Ala Trusina.

Esteemed colleagues from reNEW elected members of EMBO

The Novo Nordisk Foundation Center for Stem Cell Medicine is proud to announce that CEO and Executive Director of reNEW, Professor Mellissa H. Little and Principal Investigator at reNEW’s Copenhagen node, Professor Joshua Brickman, have this year been elected members of the prestigious European Molecular Biology Organization – EMBO.

4M euros for research into nuclear metabolism

Associate Professor Jan Żylicz from reNEW Copenhagen node, as part of an international consortium, has been awarded an MSCA Doctoral Networks Grant for project; NUCLEAR – metabolic regulation of genome function and cell identity.

The Serup Group in Copenhagen break new ground on the development of a stem cell therapy to treat diabetes

Assistant Professor Philip Seymour, former Assistant Professor Nina Funa and PhD student Heidi Mjøseng, with colleagues from the Serup Group at the Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, have had a paper published in Stem Cell Reports investigating further development of a cellular therapy to replace the lost insulin-producing beta cells in type one diabetics.