Abstract
BackgroundIn type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin. To be successful, this procedure has to address the problems caused by the immune and autoimmune responses to the graft. Islet encapsulation using various techniques and materials has been and is being extensively explored as a possible approach. Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets.MethodsTo improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets in general and of micro-encapsulated islets in particular, we performed dynamic perifusion experiments with frequent sampling. We used unencapsulated and microencapsulated murine islets in parallel and fitted the results with a complex local concentration-based finite element method (FEM) computational model.ResultsThe high-resolution dynamic perifusion experiments allowed good characterization of the first-phase and second-phase insulin secretion, and we observed a slightly delayed and blunted first-phase insulin response for microencapsulated islets when compared to free islets. Insulin secretion profiles of both free and encapsulated islets could be fitted well by a COMSOL Multiphysics model that couples hormone secretion and nutrient consumption kinetics with diffusive and convective transport. This model, which was further validated and calibrated here, can be used for arbitrary geometries and glucose stimulation sequences and is well suited for the quantitative characterization of the insulin response of cultured, perifused, transplanted, or encapsulated islets.ConclusionsThe present high-resolution GSIR experiments allowed for direct characterization of the effect microencapsulation has on the time-profile of insulin secretion. The multiphysics model, further validated here with the help of these experimental results, can be used to increase our understanding of the challenges that have to be faced in the design of bioartificial pancreas-type devices and to advance their further optimization.Electronic supplementary materialThe online version of this article (doi:10.1186/s12938-015-0021-9) contains supplementary material, which is available to authorized users.
Highlights
In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin
To accurately quantify the effect that microencapsulation has on the time-profile of insulin secretion from isolated islets, we first performed high-resolution parallel perifusion experiments with unencapsulated and alginate-encapsulated murine islets
Overall, the high-resolution experimental results collected are in agreement with previous results [32,41,42,46], whereby the glucose-stimulated insulin release (GSIR) response of alginate microencapsulated islets in perifusion experiments was found to be similar to that of free islets, but somewhat delayed and blunted – a difference that increases with increasing capsule thickness
Summary
In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin To be successful, this procedure has to address the problems caused by the immune and autoimmune responses to the graft. It is an algae-derived or seaweed-derived anionic polysaccharide comprised of unbranched polymers of 1,4-linked β-D-mannuronic and α-L-guluronic acid residues, which form a gel in the presence of multivalent cations such as Ca2+ or Ba2+ Such approaches have their own challenges: for example, failed clinical and preclinical attempts [11,12] make it clear that minimizing the volume of encapsulating material and the corresponding diffusional limitations are crucial for graft success
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