Transplantation of alginate microcapsules: generation of antibodies against alginates and encapsulated porcine islet-like cell clusters.
BACKGROUND
Microencapsulation of islets of Langherhans in alginate poly-L-lysine capsules provides an effective protection against cell-mediated immune destruction, and ideally should allow the transplantation of islets in the absence of immunosuppression. It has previously been suggested that alginate rich in mannuronic acid (high M) is more immunogenic than alginate rich in guluronic acid (high G). The ability of these alginates to induce an antibody response in the recipient or act as an adjuvant to antibody responses against antigens leaked from the capsule was investigated in the present study.


METHODS
Empty capsules made from these different types of alginate were transplanted intraperitoneally to Wistar rats or Balb/c mice. In addition, some animals were also injected with bovine serum albumin to assess the ability of the alginates to act as an adjuvant to this antigen. Antibody responses to intraperitoneally transplanted free and microencapsulated fetal porcine islet like cell clusters (ICC) were also evaluated, in animals treated with or without cyclosporine.


RESULTS
Antibodies against high M-alginate capsules were detected in the sera of mice transplanted with this capsule type. However, this response was not seen after the transplantation of high G capsules. When Wistar rats were used as recipients, no antibody responses were detected against any type of alginate capsules. Neither type of capsule acted as an adjuvant. Antibodies against ICC were present, in rats transplanted with both nonencapsulated and encapsulated ICCs. Administration of cyclosporine could abolish this production of antibodies against ICC.


CONCLUSIONS
High G-alginate capsules are less immunogenic than high M capsules. Because encapsulation did not protect against the generation of antibodies against ICC, it can be assumed that antigen leakage from the capsules occurs, as no evidence was found for capsules breaking in vivo.
Kulseng
B
B
Institute of Cancer Research and Molecular Biology, Norwegian Institute of Science and Technology, Trondheim.
Skjåk-Braek
G
G
Ryan
L
L
Andersson
A
A
King
A
A
Faxvaag
A
A
Espevik
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000464:Alginates / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000032:analysis; D001672:Biocompatible Materials / Q000494:pharmacology; D002214:Capsules; D002449:Cell Aggregation / Q000502:physiology; D005260:Female; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000166:cytology / Q000502:physiology; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007515:Islets of Langerhans / Q000196:embryology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000276:immunology; D013552:Swine / Q000196:embryology; D014183:Transplantation, Heterologous / Q000379:methods*
D000276:Adjuvants, Immunologic; D000464:Alginates; D000906:Antibodies; D001672:Biocompatible Materials; D002214:Capsules; D006603:Hexuronic Acids; D012710:Serum Albumin, Bovine; D020723:Glucuronic Acid