Purpose:

To determine the impact of CXCL12 on vascularization and immune response to xeno islets transplanted into TheraCyte macroencapsulation device in diabetic C57BL/6 mice.

Materials and Methods:

Three study arms were tested to determine how CXCL12 impacts graft survival, macroencapsulation device vascularization and localized anti-xeno immune response. Empty TheraCyte devices were attached to CXCL12-containing Alzet pumps with a 28 gauge flexible catheter and implanted into C57BL/6 mice and allowed to vascularize for 4 weeks. Diabetes was induced with streptozotocin 1-week prior to islet implant. After diabetes had been successfully induced and the 4-week vascularization was complete, the TheraCyte port was exposed and a slurry of 1.6% sodium alginate, 1ug/mL CXCL12, and 1,000 IEQ of porcine islets were implanted into the lumen of the TheraCyte devices. Blood glucose and porcine C –peptide was then monitored to determine graft viability. Devices were explanted 4-weeks after islet implant to determine vascularization and immune response to the macroencapsulation xeno islets. Explanted devices were cryopreserved and fluorescently stained to quantify insulin expression in islet graft along with vasculature, and localized immune response with fibroblasts, macrophage subpopulations, CD3, CD4, CD8 and FOXP3 staining on the tissue surrounding the TheraCyte device.

Results:

Euglycemia was achieved in all mice where devices contained xenoislets, demonstrating successful application of combined TheraCyte macroencapsulation and CXCL12-eluting Alzet osmotic pump. Xeno islet encapsulation with CXCL12 suggests increased vascularization and reduced immune response to xeno islets. Preliminary analysis of TheraCyte device vascularization suggests a positive trend of increased vasculature in CXCL12+ implants and further study of vascularization and immune response will be completed once devices are explanted in fully powered ongoing studies.

Summary of Conclusions:

Preliminary data supports the idea that a combined macroencapsulation device and CXCL12-eluting Alzet pump protects and supports the function of contained xenoislets. CXCL12 appears to act as an immune-repellent and further promotes vascularization in macroencapsulation.

CITATION INFORMATION: Penson M, Sremac M, Sirbulescu R, Brauns T, Harrington F, Poznansky M. CXCL12 Modulation of Localized Immune Responses to Subcutaneous Islet Macrocapsulation. Am J Transplant. 2017;17 (suppl 3).

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