07 December 2018

DanStem takes next Step in Developing Insulin-Producing Cells from Stem Cells

stem cells

Researchers from the Novo Nordisk Foundation Center for Stem Cell Biology have uncovered new signals that control the maturation of immature stem cells in the pancreas. This may greatly affect future treatments for especially type 1 diabetes. The study has just been published in the journal of repute Nature.

Photo: Caitlin Collin.  

A year ago, researchers from the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) managed to describe how so-called endocrine progenitor cells – immature stem cells destined to become hormone-producing cells in the pancreas – can be modified to produce insulin.

In a new study published in Nature, the same researchers solved another mystery, namely how other progenitors that give rise to the endocrine progenitors and later hormone-producing cells and epithelial cells responsible for building the ducts of the pancreas are instructed into these two cell fates. 

By cultivating single human progenitor cells on so-called micro-patterned glass plates, the researchers discovered that their decision to become either a duct or an insulin-producing cell is regulated by mechanical influences in their environment. The study further shows that proteins in the progenitor cells’ surrounding connective tissue determine whether they develop into insulin-producing cells or organ-building cells. Specifically, if the cells are exposed to a certain type of signals in the so-called extracellular matrix, they develop into duct cells, and if they are exposed to a different type of extracellular matrix, they develop into endocrine insulin-producing beta cells.

‘Our discovery is groundbreaking because it explains how multipotent progenitor cells mature into various cell types during the organ formation. It also gives us the tools to reproduce the process in the laboratory and thus more accurately reconstruct cells that have been lost or damaged due to serious diseases such as type 1 diabetes. This means we can now more accurately produce insulin-producing beta cells from human pluripotent stem cells for future clinical trials in type 1-diabetes patients", says Professor and Executive Director at the Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, at the University of Copenhagen Henrik Semb explains. Henrik Semb is also the Director of the Institute of Translational Stem Cell Research at the Helmholtz Zentrum in Munich.

The study is funded by Novo Nordisk Foundation, Lundbeck Foundation, the European Commission via the project HumEn, the Independent Research Fund Denmark and the Danish Council for Strategic Research. Drs. Anant Mamidi and Postdoc Christy Prawiro are both first authors of the study, which is a result of their cooperation with Professor Palle Serup’s research group at DanStem. Anant Mamidi and Henrik Semb have applied for an international patent based on the study.

Scientific article: ‘Mechanosignaling via integrins directs pancreatic progenitor fate decisions’ has been published in Nature by Henrik Semb, Professor and Executive Director, Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen, and head of Institute of Translational Stem Cell Research at Helmholtz Zentrum München is last author. Drs. Anant Mamidi, Assistant Professor, DanStem and Christy Prawiro DanStem share first authorship, and the work is the result of a collaboration with Professor Palle Serup's group.

Contact information

Professor Henrik Semb
Novo Nordisk Foundation Center for Stem Cell Biology 
Mail: semb@sund.ku.dk
Telephone: +45 23 48 11 48