Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance

Gerace D, Zhou Q, Kenty JH, Veres A, Sintov E, Wang X, Boulanger KR, Li H, Melton DA.
Cell Rep Med. 2022 Dec 22:100879. doi: 10.1016/j.xcrm.2022.100879. PMID:36599351

Of Interest Revisiting the Pattern of Loss of β-Cell Function in Preclinical Type 1 Diabetes Unveiling islet heterogeneity using an automated microfluidic imaging system Droplet-based fluorescence anisotropy insulin immunoassay Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of Type 1 Diabetes Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes The Teplizumab Saga: The Challenge of Not Getting Lost in Clinical Translation Rebalancing the Immune System to Treat Type 1 Diabetes Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice Serum from pregnant donors induces human beta cell proliferation Glucagon-producing α-cell transcriptional identity and reprogramming towards insulin production Harnessing regulatory T cells to establish immune tolerance Repositioning the Early Pathology of Type 1 Diabetes to the Extraislet Vasculature Impaired islet function with normal exocrine enzyme secretion is consistent across the head, body, and tail pancreas regions in type 1 diabetes Low-Dose Antithymocyte Globulin: A Pragmatic Approach to Treating Stage 2 Type 1 Diabetes Sox9 regulates alternative splicing and pancreatic beta cell function Paracrine signalling by pancreatic δ cells determines the glycaemic set point in mice Bridging the Gap: Pancreas Tissue Slices From Organ and Tissue Donors for the Study of Diabetes Pathogenesis Decrease in multiple complement proteins associated with development of islet autoimmunity and type 1 diabetes PTPN2 regulates metabolic flux to affect beta cell susceptibility to inflammatory stress Extensive elimination of acinar cells during normal postnatal pancreas growth Diabetes Study of Children of Diverse Ethnicity and Race: Study design Golden age of immunoengineering Regulatory approval of islet transplantation for treatment of type 1 diabetes: Implications and what is on the horizon Stem cell-derived islet therapy: is this the end of the beginning? Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas A structural blueprint for interleukin-21 signal modulation Loss of ZNF148 enhances insulin secretion in human pancreatic β cells Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space Single-nucleus multi-omics of human stem cell-derived islets identifies deficiencies in lineage specification Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice Matters arising: Insufficient evidence that pancreatic β cells are derived from adult ductal Neurog3-expressing progenitors The Extra-Islet Pancreas Supports Autoimmunity in Human Type 1 Diabetes Longitudinal MRI Shows Progressive Decline in Pancreas Size and Altered Pancreas Shape in Type 1 Diabetes Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies Exocrine Proteins Including Trypsin(ogen) as a Key Biomarker in Type 1 Diabetes Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways Identifying type 2 diabetes risk genes by β-cell CRISPR screening Targeted delivery of harmine to xenografted human pancreatic islets promotes robust cell proliferation Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells Hypothesis: Induction of Autoimmunity in Type 1 Diabetes-A Lipid Focus Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes IL18 signaling causes islet β cell development and insulin secretion via different receptors on acinar and β cells
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