Diabetes mellitus encompasses a heterogeneous group of metabolic disorders defined by abnormalities in insulin secretion, function, or both. Exogenous insulin therapy has long been the principal treatment strategy for patients with type 1 diabetes and for those in advanced stages of type 2 diabetes. Stem cell therapy has gained significant attention in recent years as a potential curative approach for several life-threatening disorders. In this review, we focus on the use of induced pluripotent stem cells as an alternative source for beta-cell generation, offering a solution to organ scarcity and providing a sustainable supply of insulin-producing cells. We further evaluate current developments in encapsulation technologies and transplantation sites, while noting that the issue of immune-mediated graft rejection continues to be widely debated. The aim of this review is to outline encapsulation techniques and transplantation approaches explored in animal models, and to discuss the risks and challenges anticipated in human clinical trials.

This study investigated the potential allergenicity of sporopollenin exine capsule preparations (SpECs) derived from plant pollen or spores as allergenicity could limit their use as a therapeutic oral drug delivery system. As allergenicity may differ depending on the method of preparation, raw spores from Lycopodium clavatum, together with 6 L. clavatum SpEC preparations were evaluated in vitro by adenosine triphosphate (ATP) bioassay for cell viability. Subsequently, in vivo evaluations were performed in 6–8 week male Balb/C mice gavaged daily with raw L. clavatum spores, a negative control (PBS), or one of SpEC-3, 4 or 5 preparations for five consecutive days; gastrointestinal tissues were collected 6 hours following the final gavage. In vitro cytotoxicity studies showed that, compared to the cell control, L. clavatum spores and SpEC-2 and SpEC-4 preparations showed significantly decreased cell viability, while no significant differences in cell viability were found for SpEC-1, 3, 5 or 6 preparations, all of which were extracted more intensively than SpEC-2 or SpEC-4 preparations. In vivo safety studies showed no increase in CD68-positive macrophage cell infiltration in any region of the gastrointestinal tract (stomach, duodenum, jejunum, ileum or colon), liver or kidneys. No exines were found in any tissue. We concluded that, whilst differing SpEC manufacturing processes may have residual in vitro cytotoxicity, this did not translate to an acute in vivo oral gastrointestinal immune response, suggesting their safety as a vehicle for gastrointestinal pharmaceutical delivery.

Endothelial dysfunction has been reported in polyendocrine metabolic ovarian syndrome (PMOS) and is associated with obesity. We hypothesised that circulating biomarkers of endothelial dysfunction would not differ between non-obese women with PMOS and age- and BMI-matched controls in the absence of major between-group differences in insulin resistance (IR), systemic inflammation or vitamin D status. Plasma concentrations of 20 endothelial-associated proteins were measured using Slow Off-rate Modified Aptamer (SOMAscan) technology in 29 non-obese women with PMOS and 29 age- and BMI-matched controls. Women with PMOS had higher Ferriman–Gallwey scores, free androgen index (FAI) and anti-Müllerian hormone (AMH), whereas HOMA-IR, C-reactive protein (CRP), vitamin D metabolites and endothelial-associated biomarkers did not differ significantly between groups. Within the PMOS cohort, FAI was strongly positively associated with E-selectin (Pearson r = 0.718, p < 0.001, FDR-adjusted q = 0.027), and HOMA-IR was positively associated with ICAM-2 (r = 0.670, p = 0.001, q = 0.046). The FAI–E-selectin association remained robust in Spearman sensitivity analysis (ρ = 0.720, p < 0.001, q = 0.009), whereas the HOMA-IR–ICAM-2 association remained nominally significant (ρ = 0.579, p = 0.007) but not after FDR correction. A positive association between 24,25(OH)₂D₃ and tumour necrosis factor (TNF) was observed using Pearson correlation (r = 0.648, p = 0.002, q = 0.042), but was not retained after FDR correction in Spearman sensitivity analysis. Thus, non-obese women with PMOS did not demonstrate a generalised alteration in circulating endothelial biomarkers compared with matched controls. Hyperandrogenism, in particular, was robustly associated with endothelial activation, whereas associations with IR were less consistent and vitamin D metabolites showed no robust relationship with the endothelial biomarker profile. Collectively, the findings suggest that variation in endothelial activation in non-obese PMOS is more closely associated with metabolic dysfunction and androgen excess than with circulating vitamin D status, while the cross-sectional design precludes inference regarding causality.