Pancreatic islet PEGylation as an immunological polymeric restraint

Abstract

Pancreatic islet transplantation is one of the most promising strategies for patients suffering from type 1 diabetes mellitus, but several therapeutic immunosuppressive medications must be administered to protect transplanted islets in the long-term and these expose patients to the risk of serious complications. Therefore, it is necessary to attenuate or eliminate the usage of immunosuppressant. Here, we introduce pancreatic islet PEGylation technique on the surface of islets to reduce immunogenicity of transplanted islets, thereby reducing dosage of immunosuppressive medicines. In addition, various strategies are tried to show the synergistic effect of the conjugated PEG molecules on the prevention of immunoisolation and induction of immune tolerance. This review critically addresses various insights developed in each individual strategy. © KSBB hÉóïçêÇëW=é~åÅêÉ~íáÅ=áëäÉíI=mbdóä~íáçåI=Çá~ÄÉíÉë=ãÉääáíìëI=íê~åëéä~åí~íáçåI=áããìåçéêçíÉÅíáçå= = = = =

Beta Cell Replacement Therapy

“…The encapsulation method is limited by bioincompatibility and biodegradation of the materials in addition to hypoxic damage to the islets (Lee & Byun, 2010). Further there is the practical limitation of size; the typical islet diameter of 150 µm is often increased by as much as 5 fold, leading to a volume increase greater than 100 fold.…”

Comparison of surface modification chemistries in mouse, porcine, and human islets

“…Immunoisolation has been primarily focused on macroencapsulation (multiple islets within a capsule) and microencapsulation (individual islets encapsulated) using alginate gels . However, these strategies result in concomitant increases in islet volume, which can result in hypoxic damage due to poor oxygen and nutrient diffusion, and which may require the use of alternative transplant sites . Islet surface modification with the biologically inert, hydrophilic, long‐chain polymer polyethylene glycol (PEG) has emerged as a nanoencapsulation technique that may avoid many of the issues of gel encapsulation while creating a functional nanoscale immunological barrier .…”

“…However, these strategies result in concomitant increases in islet volume, which can result in hypoxic damage due to poor oxygen and nutrient diffusion, and which may require the use of alternative transplant sites . Islet surface modification with the biologically inert, hydrophilic, long‐chain polymer polyethylene glycol (PEG) has emerged as a nanoencapsulation technique that may avoid many of the issues of gel encapsulation while creating a functional nanoscale immunological barrier . For example, PEGylation of islet surfaces using N‐hydroxysuccinimide (NHS)–functionalized PEG has resulted in long‐term allogenic graft survival with reduced use of systemic immunosuppressants .…”

“…[14][15][16] Islet surface modification with the biologically inert, hydrophilic, long-chain polymer polyethylene glycol (PEG) has emerged as a nanoencapsulation technique that may avoid many of the issues of gel encapsulation while creating a functional nanoscale immunological barrier. 14…”

Optimization of monomethoxy poly(ethylene glycol) grafting on Langerhans islets capsule using response surface method

“…However, immune destruction of transplanted islets is an impediment for a successful procedure (Devos et al 2005). There are two major approaches to immunoisolate islets: islet encapsulation and surface modification (Lee and Byun 2010). Conjugation of polyethylene glycol (PEG) to the surface of Langerhans islets, islet PEGylation, is another novel approach for immunoprotection of the islets (Panza et al 2000; Scott and Chen 2004).…”