*PATRICK VERMETTE

Development of a New Matrix for Pancreatic Islets Culture and its Validation in a Bioartificial Pancreas

Challenge: Islet transplantation is an efficient therapy to reverse type 1 diabetes. However, the long-term function of the graft is not ensured, and the problem of autoimmunity remains. An interesting alternative consists of a bioartificial pancreas in which islets are encapsulated. However, the islet environment within such a pancreas still needs to be improved to better preserve islet survival and function. Optimizing this environment is essential to develop a suitable tissue engineering strategy to replace the non-functional islets present in type 1 diabetes patients.

Solution: The team has developed two complementary approaches. The first one was designed to assess the viability and functionality of pancreatic cells on modified surfaces composed of peptides and extracellular matrix (ECM) molecules. In this assay, hyaluronic acid-modified scaffolds had a positive influence on viability, cell number and insulin content in pancreatic beta cells and primary islets. In parallel, a 3D environment that could sustain pancreatic tissue viability and functionality (an artificial pancreas) was investigated.

Achievements/Impact: The team has developed an artificial pancreas (miniaturized alginate beads used as an embedding matrix) which was implanted in rats as small pockets (ten beads each and 4 pockets/animal). This artificial pancreas was validated by investigating the effect of hyaluronic acid and vascular endothelial growth factor on the viability, insulin presence, and function after implantation. In these conditions, hyaluronic acid resulted in a three times higher presence of insulin-positive beads, while further addition of vascular endothelial growth factor significantly increased the metabolic activity in/around the beads but did not affect the amount of insulin-producing beads. The industry can now use this platform to screen drug candidates in a high-throughput assessment to identify candidates that are suitable for further development.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigators:


Patrick Vermette
Université de Sherbrooke

Séverine Sigrist
Centre européen d’étude du diabète en France (CeeD)

Co-investigator

Richard Bou Aoun
Defymed, France

Completed Project
$ 1,093,900 / 3 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• MEI
• BL-NCE
 
And by co-funding partners:
• Alsace BioValley
• Defymed