Dataset Information

Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes.

ABSTRACT: Type 1 diabetes (T1DM) affects one in every 400 children and adolescents in the US. Due to the limitations of exogenous insulin therapy and whole pancreas transplantation, pancreatic islet transplantation has emerged as a promising therapy for T1DM. However, this therapy is severely limited by donor islet availability and poor islet engraftment and function. We engineered an injectable bio-synthetic, polyethylene glycol-maleimide hydrogel to enhance vascularization and engraftment of transplanted pancreatic islets in a mouse model of T1DM. Controlled presentation of VEGF-A and cell-adhesive peptides within this engineered material significantly improved the vascularization and function of islets delivered to the small bowel mesentery, a metabolically relevant site for insulin release. Diabetic mice receiving islets transplanted in proteolytically degradable hydrogels incorporating VEGF-A exhibited complete reversal of diabetic hyperglycemia with a 40% reduction in the number of islets required. Furthermore, hydrogel-delivered islets significantly improved weight gain, regulation of a glucose challenge, and intra-islet vascularization and engraftment compared to the clinical standard of islet infusion through the hepatic portal vein. This study establishes a simple biomaterial strategy for islet transplantation to promote enhanced islet engraftment and function.

SUBMITTER: Phelps EA

PROVIDER: S-EPMC3628538 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes.

Phelps Edward A EA Headen Devon M DM Taylor W Robert WR Thulé Peter M PM García Andrés J AJ

Biomaterials 20130326 19

Type 1 diabetes (T1DM) affects one in every 400 children and adolescents in the US. Due to the limitations of exogenous insulin therapy and whole pancreas transplantation, pancreatic islet transplantation has emerged as a promising therapy for T1DM. However, this therapy is severely limited by donor islet availability and poor islet engraftment and function. We engineered an injectable bio-synthetic, polyethylene glycol-maleimide hydrogel to enhance vascularization and engraftment of transplante ...[more]

PMID: 23541111

Similar Datasets

Project description:BackgroundPancreatic Islets of Langerhans are heterogeneous tissues consisting of multiple endocrine cell types that carry out distinct yet coordinated roles to regulate blood glucose homeostasis. Islet dysfunction and specifically failure of the beta cells to secrete adequate insulin are known precursors to type 2 diabetes (T2D) onset. However, the exact genetic, (epi)genomic, and environmental mechanisms that contribute to islet failure, and ultimately to T2D pathogenesis, require further elucidation.Scope of reviewThis review summarizes efforts and advances in dissection of the complex genetic underpinnings of islet function and resilience in T2D pathogenesis. In this review, we will highlight results of the latest T2D genome-wide association study (GWAS) and discuss how these data are being combined with clinical measures in patients to uncover putative T2D subtypes and with functional (epi)genomic studies in islets to understand the genetic programming of islet cell identity, function, and adaptation. Finally, we discuss new and important opportunities to address major knowledge gaps in our understanding of islet (dys)function in T2D risk and progression.Major conclusionsGenetic variation exerts clear effects on the islet epigenome, regulatory element usage, and gene expression. Future (epi)genomic comparative analyses between T2D and normal islets should incorporate genetics to distinguish patient-specific from disease-specific differences. Incorporating genotype information into future analyses and studies will also enable more precise insights into the molecular genetics of islet deficiency and failure in T2D risk, and should ultimately contribute to a stratified view of T2D and more precise treatment strategies. Islet cellular heterogeneity continues to remain a challenge for understanding the associations between islet failure and T2D development. Further efforts to obtain purified islet cell type populations and determine the specific genetic and environmental effects on each will help address this. Beyond observation of islets at steady state conditions, more research of islet stress and stimulation responses are needed to understand the transition of these tissues from a healthy to diseased state. Together, focusing on these objectives will provide more opportunities to prevent, treat, and manage T2D.

Dataset Information

Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes.

Publications

Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets