[Correction of a diabetes mellitus type 1 on primate with encapsulated islet of pig pancreatic transplant].
The allogeneic transplantation of pancreatic islet cells into diabetic patients is severely restricted by the recurrent lack of organs. To the lack of donors is added the fact that several pancreas donors are often needed in order to treat a single diabetic recipient. Another source of cells that can produce insulin would therefore be of major interest. The pig constitutes a possible option to be taken seriously. Nonetheless, grafting pig islets might prove difficult because of the species barrier. The principal obstacle to the xenotransplantation of cells remains the necessity for powerful immunosuppression, probably inapplicable in man. Therefore, we have centred our work around the encapsulation of islets in order to evaluate the possibility of using pig cells without immunosuppression. (1) This experimental work first evaluated the influence of the age of the pig (young versus adult pigs) on the size of the islets, the collagen and the vascular structures. Adult donor pigs were selected. (Dufrane et al., Pancreas 30(2), 2005). (2) After deciding on the age, all the parameters involved in the removal of the pancreas and the procedures of isolating the pig islets were scrutinized by multivariable analysis. (Dufrane et al., Xenotransplantation 13(3), 2006). (3) Before evaluating the effect of encapsulation on the pig islets in diabetic monkeys, the biocompatibility of an alginate membrane was first evaluated in a non-diabetic primate model without immunosuppression. The long term stability and biocompatibility of pig islets encapsulated in alginate have been confirmed for up to six months after implantation under the renal capsule. A small proportion of these encapsulated pig islets not only survived for six months but remained capable of reacting in vitro to stimulation with glucose + forskolin, thus demonstrating preserved endocrine function. This in vivo experience has enabled us to identify the most important parameters for successful encapsulation. (Dufrane et al., Transplantation 81(9), 2006; Dufrane et al., Biomaterials 27(17), 2005). We then (4) investigated the most appropriate means of inducing irreversible diabetes in primates: a low dose (50 mg/kg) of streptozotocine (STZ) permanently destroys more than 97% of the insulin-producing cells of the pancreas, without any side effects on hepatic or renal function. (Dufrane et al., Transplantation 81(1), 2006 (5) After induction of diabetes by STZ in primates, the capacity of encapsulated pig islets to control diabetes after transplantation was evaluated both under the renal capsule and in the form of a graft of a monolayer of cells in the subcutaneous space. The second technique enabled the diabetic status to be controlled for at least six months without any immunosuppression in four primates. This result is unique since only major immunosuppressant regimes have so far brought comparable results.
Gianello
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Dufrane
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D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology / Q000601:surgery*; D004195:Disease Models, Animal; D006085:Graft Survival; D000882:Haplorhini; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D015999:Multivariate Analysis; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology / Q000379:methods*; D016896:Treatment Outcome