Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.

Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression.

Coagulation, inflammation, and CD46 transgene expression in neonatal porcine islet xenotransplantation.

Background: Thrombosis is a known consequence of intraportal islet transplantation, particularly for xenogeneic islets. To define the origins of thrombosis after islet xenotransplantation and relate it to early inflammation, we examined porcine islets transplanted into non-human primates using a dual-transplant model to directly compare islet characteristics.

Methods: α1,3-Galactosyltransferase gene-knockout (GTKO) islets with and without expression of the human complement regulatory transgene CD46 (hCD46) were studied.

Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model.

Sensitized patients are difficult to transplant due to pre-formed anti-donor immunity. We have previously reported successful desensitization using carfilzomib and belatacept in a non-human primate (NHP) model. Here we evaluated selective blockade of the co-stimulatory signal (CD28-B7) with Lulizumab, which preserves the co-inhibitory signal (CTLA4-B7).

Soft Tissue Anchoring Performance, Biomechanical Properties, and Tissue Reaction of a New Hernia Mesh Engineered to Address Hernia Occurrence and Recurrence.

One opportunity to reduce hernia occurrence and recurrence rates (currently estimated to be 30% at 10 years postoperatively) is by enhancing the ability of hernia meshes to anchor into tissue to prevent mesh migration, mesh contraction, and mesh tearing away from tissue. To address this, we developed a novel moderate-weight, macroporous, polypropylene mesh (termed the T-line mesh) with mesh extensions to optimize anchoring. We examined the physical properties, biomechanical performance, and biocompatibility of this novel mesh versus a predicate mesh anchored with #0-suture.

Th17 cell inhibition in a costimulation blockade-based regimen for vascularized composite allotransplantation using a nonhuman primate model.

Vascularized composite allotransplantation (VCA) is challenged by the morbidity of immunosuppression required to prevent rejection. The use of highly specific biologics has not been well explored in VCA. Given that psoriasis is T-cell mediated, as is rejection of skin-containing VCAs, we sought to assess the role of ustekinumab and secukinumab, which are approved to treat psoriasis by inhibiting Th17 cells.