Introduction The purpose of this study is to determine whether a clinical-grade alginate-microencapsulant incorporating CXCL12, can protect and sustain the function of allo and/or adult porcine islets in non-diabetic and ultimately, diabetic non-human primates (NHPs). If these pilot studies are successful they could enable pivotal NHP studies to ultimately support an IND application. Materials and Methods Alginate microcapsules with or without CXCL12 were transplanted into the intraperitoneal cavity of healthy NHPs to examine the inflammatory and immune responses to the alginate alone. The reaction to these “blank” capsules was assessed by cytokine assay, flow cytometry, histology and immunohistochemistry at day 30, 100 and 180 post transplant. We then examined transplantation of autologous or allogeneic NHP islets microencapsulated in alginate incorporating CXCL12 into healthy NHPs. We examined explant islet function and immune responses to transplanted islets at 30 and 100 days post transplant. Results and Discussion Studies of blank capsule transplants revealed a minimal cytokine, immune and cellular reaction. Intact capsules were readily retrieved from the intraperitoneal cavity by lavage at 30, 100 and 180 days post transplant. Capsules containing CXCL12 when found adjacent to mesentery were not surrounded by inflammatory cells in marked contrast to capsules without CXCL12 which were consistently surrounded by a significant inflammatory and fibrotic reaction. Two autologous encapsulated islet transplants with CXCL12 were performed revealing retrievable capsules at 30 days post transplantation with minimal surrounding infiltration. Studies of the inflammatory and immune responses to these capsules are under way. Retrieved encapsulated islets were functional at 30 days post transplantation. Alloislet transplant studies are ongoing at this time.

Conclusions The primary finding to date is that alginate microcapsules containing CXCL12 or auto islets were retrieved and demonstrated functionality and induced a minimal inflammatory or immune response. These data support the next step in our project including allo and xeno transplantation into non diabetic NHPs.

CITATION INFORMATION: Sremac M, Saraya A, Clemente O, Penson M, Chavan S, Chronos N, Schuetz C, Lei J, Markmann J, Brauns T, Poznansky M. CXCL12 as Innovative Immune Isolating Chemokine for Microencapsulated Allo and Xeno-Transplantation in NHPs. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress