Rapid failure of pig islet transplantation in non human primates.
We have previously demonstrated that adult pig islets of Langerhans are not destroyed in vitro by primate sera. Whether these islets can function when placed into the liver of non-human primates is not known. We now report on the outcome of pig islet xenotransplantation into five non diabetic primates (four baboons and one macacus fascicularis) receiving intraportally purified adult pig islets. The average number of islet-equivalent per graft was 110,000 (60-180,000). All animals received associations of ATG, cyclosporine or LF 195 (a deoxyspergualin analog), mycophenolate mofetil and corticosteroids. A specific porcine C-peptide (C-pep) RIA test was used to monitor insulin secretion. Two hours after grafting, porcine C-peptide was positive (from 0.37 to 4.25 ng/ml) in all monkeys except one. Primate C-pep was normal in all cases. Only two monkeys had detectable levels of porcine C-pep on day 1 or 2 with undetectable levels thereafter, even after glucagon challenge between days 6 and 10. Several normal islets with moderate inflammatory infiltration were observed in one animal liver on day 2 (the time of necropsy) as well as islets with IgM and complement deposition. Among animals sacrificed on days 14, 16 and 38, some residual islet cells could be identified only in livers collected on day 14. Partial glycaemic control was achieved in some rats receiving islets from the same preparations. In conclusion, adult pig islets are not able to maintain insulin secretion for more than 24 h when injected intraportally into non diabetic immunosuppressed monkeys. suggesting immediate islet xenograft destruction.
Cantarovich
Diego
D
Institut de Transplantation et de Recherche en Transplantation, Centre Hospitalier Universitaire, Nantes, France. diego.cantarovich@chu-nantes.fr
Blancho
Gilles
G
Potiron
Nicolas
N
Jugeau
Nathalie
N
Fiche
Maryse
M
Chagneau
Carine
C
Letessier
Eric
E
Boeffard
Françoise
F
Loth
Philippe
P
Karam
Georges
G
Soulillou
Jean-Paul
JP
Le Mauff
Brigitte
B
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004187:Disaccharides / Q000032:analysis; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D008252:Macaca fascicularis; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010215:Papio; D011323:Primates; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology / Q000473:pathology* / Q000502:physiology
D000961:Antilymphocyte Serum; D004187:Disaccharides; D007166:Immunosuppressive Agents; D007328:Insulin; C055075:galactosyl-(1-3)galactose; D016572:Cyclosporine; D009173:Mycophenolic Acid