Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: proof of concept.
BACKGROUND
Pig islets xenotransplantation remains associated with a strong humoral and cellular xenogeneic immune responses. The aim of this study was to assess the long-term biocompatibility of alginate encapsulated pig islets after transplantation in primates.


METHODS
Adult pig islets encapsulated in alginate under optimal conditions (n=7) or not (n=5) were transplanted under the kidney capsule of nondiabetic Cynomolgus maccacus. Additional primates received empty capsules (n=1) and nonencapsulated pig islets (n=2) as controls. Capsule integrity, cellular overgrowth, pig islet survival, porcine C-peptide and anti-pig IgM/IgG antibodies were examined up to 6 months after implantation.


RESULTS
Nonencapsulated islets and islets encapsulated in nonoptimal capsules were rapidly destroyed. In seven primates receiving perfectly encapsulated pig islets, part of the islets survived up to 6 months after implantation without immunosuppression. Porcine C-peptide was detected after 1 month in 71% of the animals. The majority of grafts (86%) were intact and completely free of cellular overgrowth or capsule fibrosis. Explanted capsules, after 135 (n=2/2) and 180 (n=2/3) days, demonstrated residual insulin content and responses to glucose challenge (stimulation index of 2.2). Partial islet survival was obtained despite an elicited anti-pig IgG humoral response.


CONCLUSIONS
Optimal alginate encapsulation significantly prolonged adult pig islet survival into primates for up to 6 months, even in the presence of antibody response.
Dufrane
Denis
D
Laboratory of Experimental Surgery, Université catholique de Louvain, Faculté de Médecine, and Department of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Goebbels
Rose-Marie
RM
Saliez
Alain
A
Guiot
Yves
Y
Gianello
Pierre
P
D000464:Alginates; D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D002214:Capsules; D018929:Cell Culture Techniques / Q000379:methods; D006085:Graft Survival / Q000276:immunology*; D006648:Histocompatibility; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D008252:Macaca fascicularis; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology*
D000464:Alginates; D000910:Antibodies, Heterophile; D002214:Capsules; D007074:Immunoglobulin G; D007075:Immunoglobulin M