A High Cell-Bearing Capacity Multibore Hollow Fiber Device for Macroencapsulation of Islets of Langerhans.

Katarzyna Skrzypek,Milou Groot Nibbelink,Eelco J P De Koning,Marten A Engelse,Jolanda Liefers‐Visser,Paul De Vos,Aart Van Apeldoorn,Eleftheria Stoimenou,Dimitrios Stamatialis,Alexandra M Smink,Marcel Karperien

doi:10.1002/mabi.202000021

Abstract

Macroencapsulation of islets of Langerhans is a promising strategy for transplantation of insulin-producing cells in the absence of immunosuppression to treat type 1 diabetes. Hollow fiber membranes are of interest there because they offer a large surface-to-volume ratio and can potentially be retrieved or refilled. However, current available fibers have limitations in exchange of nutrients, oxygen, and delivery of insulin potentially impacting graft survival. Here, multibore hollow fibers for islets encapsulation are designed and tested. They consist of seven bores and are prepared using nondegradable polymers with high mechanical stability and low cell adhesion properties. Human islets encapsulated there have a glucose induced insulin response (GIIS) similar to nonencapsulated islets. During 7 d of cell culture in vitro, the GIIS increases with graded doses of islets demonstrating the suitability of the microenvironment for islet survival. Moreover, first implantation studies in mice demonstrate device material biocompatibility with minimal tissue responses. Besides, formation of new blood vessels close to the implanted device is observed, an important requirement for maintaining islet viability and fast exchange of glucose and insulin. The results indicate that the developed fibers have high islet bearing capacity and can potentially be applied for a clinically applicable bioartificial pancreas.

Highlights

Clinical islet transplantation (CIT) in the liver via the infusion of islets into the portal vein has been explored as a potential therapy for patients with type 1 diabetes.[1]
We have developed new PES/PVP multibore hollow fiber membrane for islet macroencapsulation
Material biocompatibility supports the formation of blood vessels close to the multibore fiber which is crucial for encapsulated islet survival in vivo

Summary

Introduction

Clinical islet transplantation (CIT) in the liver via the infusion of islets into the portal vein has been explored as a potential therapy for patients with type 1 diabetes.[1] CIT is associated with a high degree of islet loss due to their exposure to several stress factors within the first two weeks after intervention.[2] In addition, this is only applied in a small group of severe diabetic patients as immunosuppression has to be applied to prevent graft rejection which as such has severe side effects. Extrahepatic islet transplantation using biomaterials as an immunoprotective islet carrier could improve the outcome of the transplantation by providing a more optimal environment and potentially allow for transplantation in the absence of immunosuppression.[3] the encapsulation of pancreatic islets, or beta cells, within semipermeable membranes represents a promising strategy to immobilize transplanted islets in one location outside. M. Karperien Developmental BioEngineering Faculty of Science and Technology TechMed Centre University of Twente Enschede 7500AE, The Netherlands

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Conclusion