Reversal of diabetes in non-obese diabetic mice by xenografts of porcine islets entrapped in hollow fibres composed of polyacrylonitrile-sodium methallylsulphonate copolymer.
Intraperitoneal xenografting of islets immunoprotected by semipermeable membranes is a potential method of avoiding rejection by reversal of diabetes without immunosuppression. In this preliminary study, a xenograft of porcine islets, immunoprotected in semipermeable hollow fibres composed of a hydrogel of a polyacrylonitrile-sodium methallylsulphonate copolymer (AN 69), was used to reverse autoimmune insulin-dependent diabetes mellitus (IDDM) in the NOD mouse. A diabetic state was maintained in all 46 NOD mice which received transplants of empty fibres. Transplantation of encapsulated islets reversed the diabetic state in 37% (18/54) of the recipients. In these mice, nonfasting blood glucose concentration decreased within 24 h. Glycaemia was kept below the diabetic control range and the initial pretransplant value for 6 weeks. Recipient NOD mice suffered from the severe insulitis characteristic of clinical diabetes, confirming that reversal of the hyperglycaemic state was due solely to the xenografts. Pretransplant glycaemia was slightly (p < 0.05) higher in mice which remained diabetic after grafts of fibre-containing islets than in animals which experienced reversal of hyperglycaemia after transplantation) for the peritoneal cavity of recipients which had returned to normoglycaemia after grafting with islet-containing fibres. In all 4 cases, the islets responded to glucose during a perifusion assay. In 2 out of 4 grafts removed from mice which remained hyperglycaemic after grafting with islet-containing fibres (11, 13, 15 and 27 days after transplantation), no basal or stimulated insulin secretion was detectable. Histological sections of a total of 75 fibres retrieved from the peritoneal cavities of recipient NOD mice showed surrounding inflammation, with adherent cells, neovascularisation and fibrotic reaction. These preliminary results are promising for the continued development of this bioartificial pancreas for xenogeneic islet transplantation since they demonstrate that xenogeneic islets can survive in the autoimmune environment of the NOD mouse with spontaneous diabetes mimicking human IDDM).
Rivereau
A S
AS
Laboratory of Cellular and Molecular Immuno-Endocrinology, INRA/ENVN, University School of Medicine, Nantes, France.
Darquy
S
S
Chaillous
L
L
Maugendre
S
S
Gouin
E
E
Reach
G
G
Sai
P
P
D000180:Acrylic Resins; D000181:Acrylonitrile / Q000031:analogs & derivatives*; D000818:Animals; D001672:Biocompatible Materials; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000601:surgery*; D005782:Gels; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D013552:Swine; D014183:Transplantation, Heterologous
D000180:Acrylic Resins; D001672:Biocompatible Materials; D005782:Gels; D007328:Insulin; C016892:AN-69; D000181:Acrylonitrile