Design of Bioartificial Pancreas with Functional Micro/Nano-Based Encapsulation of Islets

Abstract

Type I diabetes mellitus (TIDM), a devastating health issue in all over the world, has been treated by successful transplantation of insulin secreting pancreatic islets. However, serious limitations such as the requirement of immunosuppressive drugs for recipient patients, side effects as a result of long-term use of drugs, and reduced functionality of islets at the transplantation site remain. Bioartificial pancreas that includes islets encapsulated within semi-permeable membrane has been considered as a promising approach to address these requirements. Many studies have focused on micro or nanobased islet immunoisolation systems and tested the efficacy of encapsulated islets using in vitro and in vivo platforms. In this review, we address current progress and obstacles for the development of a bioartificial pancreas using micro/nanobased systems for encapsulation of islets.

Current progress in stem cell therapy for type 1 diabetes mellitus

“…An appropriate encapsulation device is especially crucial for T1DM to prevent an autoimmune reaction against transplanted hPSC-derived pancreatic progeny, including allogenic grafts. Criteria to evaluate an encapsulation device should take many variables into consideration, including the biocompatibility, stability and permselectivity of the membrane, interaction with the bloodstream, availability of nutrients and oxygen, among others [101][102][103]. Studies have been performed to detect optimal materials to improve these properties and have mainly been developed for pancreatic islet transplantation.…”

“…Alginate, a scaffolding polysaccharide produced by brown seaweeds, has been widely employed by virtue of its biocompatibility [ 102 , 104 , 105 ]. Alginates are linear unbranched polymers containing β-(1 → 4)-linked d -mannuronic acid (M) and α-(1 → 4)-linked l -guluronic acid (G) residues and possess eminent gel-forming properties in the presence of polyvalent cations, such as Ca 2+ and Ba 2+ [ 103 , 106 – 108 ].…”

Hydrogel Microencapsulated Insulin-Secreting Cells Increase Keratinocyte Migration, Epidermal Thickness, Collagen Fiber Density, and Wound Closure in a Diabetic Mouse Model of Wound Healing

“…Internal cell therapies have shown improved success when cells are enclosed in a barrier that protects them from the host immune response, thereby prolonging the viability and secretory characteristics of the cells. 22–24 Subcutaneous implantation of poly(ethylene glycol) diacrylate (PEGDA)-encapsulated human islets in type I diabetic patients has shown promising results of islet function with no evidence of autoimmune reaction. 23 PEGDA encapsulation has permitted successful transplantation of xenogeneic pancreatic islet cells: when porcine islets were implanted into diabetic rats, the animals achieved normoglycemia.…”

“… 24 In fact, pancreatic islet cells encapsulated within PEGDA injected into diabetic humans and animals have successfully returned them to normoglycemia without the tissue typing required when these cells are not encapsulated. 22 , 24 …”

Encapsulated Islet Transplantation: Where Do We Stand?

“…However, in all these studies, graft survival was limited, and varied considerably, ranging from months to a few years. Furthermore, phase 1 clinical studies with encapsulated islets resulted in poor outcomes, with PFO being the major factor responsible for graft failure [67][68][69]. The factors contributing to PFO are poorly understood, and are often seen as a foreign body reaction to the alginate microcapsules or host inflammatory response to antigens shed by encapsulated tissue [70,71].…”