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Nat Metab ; 2(10): 1013-1020, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32895576

RESUMO

The intrahepatic milieu is inhospitable to intraportal islet allografts1-3, limiting their applicability for the treatment of type 1 diabetes. Although the subcutaneous space represents an alternate, safe and easily accessible site for pancreatic islet transplantation, lack of neovascularization and the resulting hypoxic cell death have largely limited the longevity of graft survival and function and pose a barrier to the widespread adoption of islet transplantation in the clinic. Here we report the successful subcutaneous transplantation of pancreatic islets admixed with a device-free islet viability matrix, resulting in long-term euglycaemia in diverse immune-competent and immuno-incompetent animal models. We validate sustained normoglycaemia afforded by our transplantation methodology using murine, porcine and human pancreatic islets, and also demonstrate its efficacy in a non-human primate model of syngeneic islet transplantation. Transplantation of the islet-islet viability matrix mixture in the subcutaneous space represents a simple, safe and reproducible method, paving the way for a new therapeutic paradigm for type 1 diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/cirurgia , Transplante das Ilhotas Pancreáticas/métodos , Tela Subcutânea/cirurgia , Animais , Diabetes Mellitus Experimental/cirurgia , Transportador de Glucose Tipo 2/biossíntese , Transportador de Glucose Tipo 2/genética , Sobrevivência de Enxerto , Xenoenxertos , Humanos , Macaca fascicularis , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Suínos
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