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Association between macrophage activation and function of micro-encapsulated rat islets
P de Vos1, I Smedema, H van Goor
1Transplantation Biology, Department of Pathology and Laboratory Medicine, Section of Medical Biology, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. p.de.vos@med.rug.nl
Diabetologia
|May 17, 2003
Summary
Macrophage activation, triggered by islet-derived factors, impairs microencapsulated islet graft function. Inhibiting this early inflammation may improve graft survival for clinical applications.
Area of Science:
- Immunology
- Transplantation Biology
- Biomaterials Science
Background:
- Microencapsulated islet graft survival is often limited, despite minimal overt inflammation.
- Cellular overgrowth on a small fraction of capsules may impact overall graft function.
Purpose of the Study:
- To investigate if cellular overgrowth on microcapsules contributes to functional limitations in encapsulated islets.
- To identify the cellular components and triggers of this overgrowth and their effect on islet function.
Main Methods:
- In vivo studies in rat recipients of allogenic microencapsulated islet grafts.
- In vitro co-culture experiments with encapsulated islets and rat macrophages.
- Analysis of cellular infiltration (ED-1, ED-2 markers) and macrophage activation (cytokine secretion).
- Assessment of encapsulated islet function via static incubation and perifusion.
Main Results:
- Activated macrophages (ED-1, ED-2 positive) were the predominant cells in capsular overgrowth.
- Islet-derived factors activated macrophages, leading to TNF-alpha and IL-1beta secretion.
- Macrophage activation correlated with a significant decrease (35%) in insulin response and slower perifusion response of encapsulated islets.
Conclusions:
- Macrophage activation, induced by islet-derived factors, negatively impacts microencapsulated islet function.
- Strategies targeting temporary inhibition of macrophage activation are proposed for clinical application.
- Focusing on the first two months post-implantation may be crucial for improving graft survival.