Journal: Frontiers in Endocrinology

Article Title: Unlocking the post-transplant microenvironment for successful islet function and survival

doi: 10.3389/fendo.2023.1250126

Figure Lengend Snippet: Therapeutic options for type 1 diabetes mellitus.

Article Snippet: Stem-Cell Derived Islets , Off-target growth Limited data Differentiation optimisation , Shapiro et al 2021 ( ) Ramzy et al 2021 ( ) .

Techniques: Injection, Control, Functional Assay, Derivative Assay

Journal: International Journal of Molecular Sciences

Article Title: Reconstructing the Islets: Advances in 3D Pancreatic Organoid Models for Functional β-Cell Replacement

doi: 10.3390/ijms27031280

Figure Lengend Snippet: Immune protection strategies for pancreatic organoid-based β-cell replacement. This schematic illustrates three complementary immune-protection paradigms applied to pancreatic organoids and stem cell-derived islet-like constructs. ( Left ) Encapsulation strategies, including micro- and macroencapsulation, physically isolate transplanted organoids from host immune cells while permitting diffusion of oxygen, nutrients, glucose, and insulin; key limitations such as diffusion constraints, hypoxia, and fibrotic foreign-body responses are indicated. ( Middle ) Hypoimmunogenic engineering approaches involve genetic modulation of immune recognition pathways, including HLA editing and expression of immune checkpoint molecules (e.g., PD-L1, CD47, HLA-E) and immunoregulatory cytokines (e.g., IL-10, TGF-β), enabling host integration but remaining vulnerable to incomplete immune evasion and natural killer cell-mediated clearance. ( Right ) An emerging hybrid strategy integrates partial encapsulation with targeted immunoengineering to enhance vascular integration, immune tolerance, and long-term graft survival.

Article Snippet: More recently, Vertex Pharmaceuticals reported promising outcomes using a stem cell-derived islet cell therapy (VX-880), where all treated T1D patients showed engraftment and glucose-responsive insulin production within 90 days, and most achieved near-complete insulin independence (11 of 12 patients reduced or eliminated insulin use, and most achieved HbA 1 c < 7.0%) [ , ].

Techniques: Derivative Assay, Construct, Encapsulation, Diffusion-based Assay, Expressing

Journal: International Journal of Molecular Sciences

Article Title: Reconstructing the Islets: Advances in 3D Pancreatic Organoid Models for Functional β-Cell Replacement

doi: 10.3390/ijms27031280

Figure Lengend Snippet: Preclinical and early clinical translation of pancreatic organoid-based β-cell replacement therapies. This schematic illustrates the translational pipeline from preclinical development to early human application of stem cell-derived pancreatic progenitors, islet-like clusters, and organoid constructs for diabetes therapy. In animal models, hPSC-derived β-like cells organized into three-dimensional organoids or scaffold-supported platforms restore glycemic control, enhance glucose-stimulated insulin secretion, and improve graft maturation and engraftment compared with conventional two-dimensional cultures. Early clinical programs using encapsulated pancreatic progenitors and fully differentiated stem cell-derived islet products demonstrate safety, engraftment, endogenous C-peptide production, and reductions in exogenous insulin requirements, although outcomes remain variable. Persistent challenges include immune protection, long-term graft durability, functional maturation, and scalable manufacturing for broad clinical translation.

Article Snippet: More recently, Vertex Pharmaceuticals reported promising outcomes using a stem cell-derived islet cell therapy (VX-880), where all treated T1D patients showed engraftment and glucose-responsive insulin production within 90 days, and most achieved near-complete insulin independence (11 of 12 patients reduced or eliminated insulin use, and most achieved HbA 1 c < 7.0%) [ , ].

Techniques: Derivative Assay, Construct, Control, Functional Assay