Magnetoencapsulated human islets xenotransplanted into swine: a comparison of different transplantation sites.

BACKGROUND: The fate of magnetically labeled, barium-gelled alginate/protamine sulfate/alginate microcapsules (APSA magnetocapsules) following xenotransplantation was assessed by magnetic resonance imaging (MRI) and histopathology.

METHODS: Magnetocapsules with and without human islets were transplanted into five different clinically accessible sites: portal vein, subcutaneous tissue, skeletal muscle, the liver and the kidney subcapsular space. The surface of APSA magnetocapsules was modified using clinical-grade heparin to mitigate an instant blood-mediated inflammatory reaction.

RESULTS: The accuracy of site-specific delivery was confirmed using a clinical 1.5T MRI setup, where the magnetocapsules appeared as distinct hypointense entities after transplantation. As proven by the Lee-White blood coagulation test, heparin-treated APSA magnetocapsules did not induce blood clotting for more than 48 h in vitro. Heparinized magnetocapsules induced innate and adaptive immune responses in vivo regardless of the transplantation sites.

CONCLUSION: We have demonstrated the feasibility of using a clinical 1.5T MRI to non-invasively detect the accuracy of APSA magnetocapsule injection into various clinically accessible transplantation sites. Among the investigated transplantation sites, the liver and kidney subcapsular space were found to be the least immuno-responsive toward xenografted magneto-encapsulated human islets.