Clinically, many candidates for islet transplantation are already immunized, which increases their risk of graft rejection. Encapsulation of pancreatic islets using the TheraCyte™ device has been shown to protect against allograft rejection in nonimmunized recipients. However, the capacity of the TheraCyte™ device to prevent rejection in immunized recipients has not yet been studied. In this study, the protective capacity of the TheraCyte™ device was evaluated in an allogeneic rat model. Lewis rats were used as islet donors, and nonimmunized (control) and alloimmunized, diabetic Wistar–Furth (WF) rats were used as recipients. Graft survival was shorter in immunized recipients than in nonimmunized recipients (mean survival, 5.3 ± 2.7 and 9.3 ± 1.6 days, respectively, p < 0.01) when nonencapsulated islets were transplanted under the kidney capsule. When islets were transplanted into the TheraCyte™ device, graft function was maintained during the 6-month study period in both immunized and nonimmunized rats. In oral glucose tolerance tests performed at 1 month after transplantation, both groups had similar insulin and blood glucose levels indicating similar metabolic functions. Volume densities and absolute volumes of tissue inside the devices 6 months after transplantation were also comparable between the two groups, indicating that both groups maintained similar amounts of endocrine tissue. A higher number of IFN-γ-producing CD8⁺ T-cells were detected in immunized WF rats compared to control WF rats transplanted with encapsulated islets. This suggests that donor-specific alloreactivity in recipient rats was sustained throughout the study period. This study suggests that the TheraCyte™ device protects islet allografts also in immunized recipients. Our results further highlight the potential for using macroencapsulation to avoid immunosuppressive therapy in clinical islet transplantation.

The current standard assays for islet product release criteria are unable to predict the outcome after clinical islet transplantation. Therefore, establishment of reliable and rapid assays enabling pre‐transplantation prediction of islet potency is warranted. In the present study, we have evaluated the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) test, the glucose‐stimulated insulin release, the loss of islets during the first 24 h in culture, and the insulin/deoxyribonucleic acid as predictive assays for the ability of isolated porcine islets to cure athymic mice with streptozotocin‐induced diabetes. From the results presented, it is concluded that the measurement of the ADP/ATP ratio was the only test that correlated with transplantation outcome. In summary, we propose that the ADP/ATP assay is worthwhile as applied to human islet transplantation and seek to validate it as a rapid and potent predictor of transplant outcome.

Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15–28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.

Islet graft survival inside macroencapsulation devices is suboptimal. We hypothesized that induction of neovascularization by preimplantation of devices would improve the physiological conditions, thereby lowering the number of islets required for cure. Several rat islets were transplanted to TheraCyte immunoprotective devices implanted subcutaneously in diabetic athymic mice. Cure rates in the groups with preimplanted devices were significantly better than in those with freshly implanted devices (375 islets: 8/8 vs. 1/6, P=0.003; 125 islets: 6/6 vs. 0/7, P=0.001). Morphometric evaluations of the 125 islet groups showed higher fractional and absolute volumes of endocrine tissue in the group with preimplanted devices (P<0.001 and P=0.035, respectively). In the following dose titration study, using preimplanted devices, as low as 50 islets cured diabetic mice (100% cure, n=6). We conclude that preimplantation significantly lowers the curative dose of macroencapsulated islets to levels resembling those of free islets transplanted under the renal capsule.