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.

Complement proteins are increased in polycystic ovary syndrome (PCOS), as are markers of inflammation, such as the C-reactive protein (CRP); however, both may be increased in obesity. We hypothesised that body mass index (BMI)-driven CRP would comparably associate with an increase in complement proteins when obesity was accounted for in non-obese women with and without PCOS. In a non-obese, non-insulin-resistant population without inflammation (24 with PCOS and 24 control women), plasma CRP was measured by immunoassay. Slow Off-rate Modified Aptamer (SOMA)-scan plasma proteomic analysis of the classical, lectin, and alternative pathway complement proteins was undertaken. BMI, insulin resistance, and CRP did not differ (p < 0.05) between the cohorts. The alternative pathway of the complement protein system was overexpressed in PCOS (p < 0.05). CRP correlated positively (p < 0.05) with alternate pathway parameters in women with and without PCOS for C3a, iC3b, Factor B, Factor H, and Factor I; in PCOS alone for C3, C3adesArg, and C3d; and in women without PCOS, for properdin. CRP did not correlate with lectin pathway C2 or MBL (p > 0.05). CRP correlated positively (p < 0.05) with C4 of the classical pathways in women with PCOS alone. Hyperandrogenemia did not correlate with CRP or complement in non-obese PCOS. BMI correlated positively with C3, C3adesArg, C3a, iC3b, Factor B, Factor H, and properdin: classical pathway proteins; C1q, C4, C5 and C5a in PCOS women; BMI only correlated negatively with C1q in non-PCOS women. Upregulation of complement proteins occur in non-obese PCOS, and CRP is positively associated with complement protein changes in both women with and without PCOS. This indicates that BMI induces changes in CRP that lead to changes in the complement pathways, particularly the alternate pathway, with increases in CRP (though still within the reference laboratory normal range) leading to upregulation of complement proteins in PCOS. This suggests an enhanced set point for CRP-induced complement protein dysregulation in PCOS.

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.