J Vasc Surg Cases Innov Tech
June 2024
Delayed presentation of recipient artery pseudoaneurysms following kidney transplantation is a rare, yet critical, complication. Although the precise etiology remains unclear, factors such as chronic steroid use, iatrogenic injuries (including vascular clamp damage during index surgery), or infections could contribute. Timely surgical intervention is imperative to prevent arterial rupture and life-threatening bleeding.
View Article and Find Full Text PDFAntibody-mediated rejection has long been known to be one of the major organ failure mechanisms in xenotransplantation. In addition to the porcine α1,3-galactose (α1,3Gal) epitope, N-Glycolylneuraminic acid (Neu5Gc), a sialic acid, has been identified as an important porcine antigen against which most humans have pre-formed antibodies. Here we evaluate GalTKO.
View Article and Find Full Text PDFBackground: Vascularized composite allografts (VCA) have demonstrated good clinical outcomes dependent on chronic immunosuppression. Previous work by our group and others supports that cotransplanted vascularized bone marrow (VBM) as a component of VCA offers immunologic protection to prolong graft survival. We aimed to characterize the requirements and potential mechanisms of VBM-mediated protection of VCA by modifying grafts through various strategies.
View Article and Find Full Text PDFBackground: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity.
View Article and Find Full Text PDFOrgan scaffold bioengineering is currently limited by the inability to effectively repopulate the scaffold with appropriately distributed functional cells. We examined the feasibility of a decellularized liver scaffold to support the growth and function of multilineage allogenic cells derived from either adult or neonatal liver cells. Cell slurries from neonatal and adult rat livers containing hepatocytes, cholangiocytes, and endothelial cells were introduced into decellularized adult rat liver scaffolds via the bile duct.
View Article and Find Full Text PDFBackground: Wild-type pigs express several carbohydrate moieties on their cell surfaces that differ from those expressed by humans. This difference in profile leads to pig tissue cell recognition of human blood cells causing sequestration, in addition to antibody-mediated xenograft injury. One such carbohydrate is N-glycolylneuraminic acid (Neu5Gc), a sialic acid molecule synthesized in pigs but not in humans.
View Article and Find Full Text PDFBackground: Specific blockade of T cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. The goal of this study is to compare results associated with 3 monoclonal antibodies directed against the CD40/CD154 T cell costimulation pathway.
Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with either IDEC-131 (humanized αCD154, n = 9), 5C8H1 (mouse-human chimeric αCD154, n = 5), or 2C10R4 (mouse-rhesus chimeric αCD40, n = 6) monotherapy using a consistent, comparable dosing regimen for 3 months after transplant.
Recent years have seen a proliferation of methods leading to successful organ decellularization. In this experiment we examine the feasibility of a decellularized liver construct to support growth of functional multilineage cells. Bio-chamber systems were used to perfuse adult rat livers with 0.
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