11 November 2015
World Diabetes Day 2015: How could stem cells help?
stem cells and diabetes
Diabetes is a common life-long condition and the number of children being diagnosed with type 1 diabetes is increasing. The symptoms can be controlled but there is no cure. There are currently no proven treatments for diabetes using stem cells, however, if beta cells could be made in the lab it could solve the problem of obtaining the right number and quality of islets for transplantation.
Diabetes is a common life-long condition and the number of children being diagnosed with type 1 diabetes is increasing. The symptoms can be controlled but there is no cure. For many, diabetes means living with daily insulin injections and the possibility of long-term damage to their health. How might stem cells help?
Research carrired out at DanStem
By recapitulating key developmental stages that occur during normal pancreas development, human pluripotent stem cells (hPSCs) can be ultimately guided into mature insulin producing beta cells. Lower panel depicts a bright field image of undifferentited hPSCs (left image) that have been directed to an intermediate stage consisting of the pancreatic progenitors (PPs, middle fluorescence image) that have the capacity to form all the cells that are found in the pancreas including the beta cells (right fluorescence image). Professor Henrik Semb and his group are currently planning a phase 1/2 trial to test the safety and efficacy of the hPSC-derived insulin expressing cells derived in our lab. Furthermore, they are working with developing methods for expanding the PPs with the purpose of using them as the starting cell population for producing beta cells.
The group headed by Professor Anne Grapin-Botton focuses on understanding the impact of cellular and organ architecture on the cells’ fate choices in the pancreas and how this information is integrated with cell signalling to control cell differentiation into more specialized cell types. The overall aim is to gain new insight into human syndromes impairing pancreas development and further guide the generation of functional, insulin producing beta cells for future cell-based Diabetes therapy. Three-dimensional (3D) architecture is important for cell differentiation in the pancreas. However, current protocols aimed at directing differentiation of embryonic stem cells into beta cells are usually applied to cells grown at the bottom of a dish in 2 dimensions. The group has been successful in developing an in vitro culture system that leads to the 3D self-organization of mini-pancreas from dispersed progenitors. Progenitor cells are early descendants of stems cells, which can expand tremendously but not indefinitely. These cells can form many pancreatic cell types.
The Serup group focuses their research on developmental biology of the pancreas with the overall aim of understanding the signalling events that regulate growth and differentiation of pancreatic cell types with special emphasis on the insulin producing beta cell. The group has a special interest in the Notch signalling pathway. Recent work from Professor Palle Serup and his group suggest that understanding the direction of signalling as well as the temporal window(s) through which Notch acts will be informative for establishing protocols for the generation of fully functional beta cells from human embryonic stem cells.
The HumEn project
DanStem is coordinating an EU FP7 collaborative project (HumEn) aiming to develop insulin-producing beta cells for use as a cell therapy treatment for diabetes in the future. There has been a progress in this area, but fully mature and transplantable beta cells that can cure diabetes have not been made yet.
To make a progress the project plans to:
- Study in detail the steps it takes to make fully mature insulin producing beta cells.
- Use this knowledge to describe the best conditions for growing betta cells.
- Create tools for identifying and growing functional beta cells including for use in the clinic
- Make the work produced by the project available and accessible to other scientists and to the European public
DanStem scientists interviews and commentaries:
- Henrik Semb's commentary: 'Making insulin producing beta cells from stem cells – how close are we?'
- Palle Serup: Ø-celler vil revolutionere diabetesbehandlingen (Islet cells will revolutionize diabetes treatment)