Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
The xenotransplantation of neonatal porcine islets (NPIs) may alleviate the shortage of islets currently limiting islet allotransplantation. However, successful implementation requires understanding of the immune elements specific to xenoislets in order to effectively modify efficacious alloislet immunosuppression. To elucidate these xenospecific processes, we applied a unique dual transplant model comparing alloislets to 1,3 galactosyltransferase knockout (GKO) xenoislets in the context of rigorous costimulation and adhesion blockade.
Equivalent islet mass from rhesus and GKO neonatal pigs were infused into contralateral hemilivers of diabetic rhesus recipients, thus allowing for side by side comparison within individual primates. Immunosuppression consisted of anti-LFA-1, anti-CD154, and CTLA-4Ig. At 7 days from transplant, livers underwent sectioning by predetermined margins and immunohistochemical staining for protein and cellular immune components. Staining was digitally quantified with Aperio Imagescope® software.
Porcine specific staining confirmed separation of GKO NPIs and AIs into distinct recipient hemi-livers. Staining for IgM, CD68 (macrophage), CD57 (NK cell), and CD3 (T cell) was stronger in GKO NPIs compared to AIs. C1q and C3d staining was variable and is being evaluated in additional replicates. Recipients demonstrated higher C4d staining in AIs than GKO NPIs. We found stronger insulin staining in AIs than GKO NPIs. Recipients had improved glucose homeostasis by the experimental endpoint.
Our dual transplant model is able to maintain separation of islet preparations 7 days after transplant, creating a highly controlled environment to objectively compare early stages of islet transplantation between two different islet phenotypes. In this experiment, we found that a rigorous costimulation/adhesion blockade regimen still permits an IgM response and cellular responses by NK cells, macrophages, and T cells directed towards GKO NPIs more than AI. Insulin production and improved glucose homeostasis was dominated by AI, likely due to higher glucose sensitivity by NHP islets and functional immaturity of NPIs this early after transplant. These data suggest a need to target elements of innate IgM and cellular immunity in order to improve xenoislet engraftment.
To cite this abstract in AMA style:Samy K, Martin B, Thompson P, Farris A, Song M, Leopardi V, Collins B, Kirk A. Identifying Barriers Specific to Xenoislets by Direct Comparison to Alloislets in a Dual Transplant Model [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/identifying-barriers-specific-to-xenoislets-by-direct-comparison-to-alloislets-in-a-dual-transplant-model/. Accessed August 18, 2019.
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