Design of a Bioartificial Pancreas

Abstract

Islet transplantation has been shown to be a viable treatment option for patients afflicted with type 1 diabetes. However, the lack of availablity of human pancreases and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for a bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that will need to be taken into consideration in order to achieve the ultimate goal of routine clinical application.

Application of a novel bioreactor for in vivo engineering of pancreas tissue

“…Tissue engineering appears to be a potential novel alternative therapy for insulin-dependent diabetes mellitus in addition to an immunosuppression-free state after transplantation, which could alleviate inevitable consequences of conventional therapies for diabetes. Islet encapsulation, which is a regenerative technology, mainly consists of packaging islet cells within a semi-permeable membrane that allows insulin, nutrients, and waste products to pass while precluding the immune response (Opara, Mirmalek-Sani, Khanna, Moya, & Brey, 2010;Vaithilingam & Tuch, 2011). Although this technique appears to obviate the requirement of immunosuppression therapy and preserve the islet cells, incompatibility of capsule material and hypoxia due to inadequate revascularization have been major obstacles in clinical studies.…”

β-cell regeneration and differentiation: how close are we to the ‘holy grail’?

“…Studies in which alginate-encapsulated islets were transplanted into mouse models of diabetes demonstrated that glucose and insulin transport steadily increased over time, lasting anywhere from 28 days to 2-3 weeks (Pareta et al 2013, Park et al 2013. Furthermore, Park et al (2013) reported a linear relationship between the number of capsules and insulin production, providing a framework to calculate the number of capsules required to fully restore blood glucose control in animals and potentially humans.…”

“…Although alginate has some desirable attributes as a capsule material, there are additional challenges related to the need to carefully balance pore size such that cells obtain the nutrients they require while remaining completely isolated from the immune system (Pareta et al 2013, Park et al 2013. Islets require relatively high concentrations of oxygen and studies have demonstrated that hypoxia has a deleterious effect on their survival and function (Dionne et al 1993).…”

Winner of the student award in the undergraduate category, 10th World Biomaterials Congress, May 17–22, 2016, Montreal QC, Canada: Evaluation of the tissue response to alginate encapsulated islets in an omentum pouch model

“…1 Pancreas transplantation achieves normoglycemia by reestablishing insulin release. 2,3 However, the dependence on immunosuppression and limited availability of pancreata indicate the need for other treatment options.…”

“…Insulin injections only delay the progression of secondary complications such as retinopathy, nephropathy, and neuropathy resulting in lowering quality and expectancy of life. 1 Pancreas transplantation achieves normoglycemia by reestablishing insulin release. 2,3 However, the dependence on immunosuppression and limited availability of pancreata indicate the need for other treatment options.…”