Prevention of nonimmunologic loss of transplanted islets in monkeys.
Am J Transplant
; 14(7): 1543-51, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24913821
ABSTRACT
The nonimmunologic loss of islets in the pre-, peri-, and early post-islet transplant periods is profound. To determine the potential role that transplantation of only a marginal mass of functioning beta cells may play in triggering late nonimmunologic graft loss, we studied the effect of treatment with alpha-1-antitrypsin (AAT) in the autologous cynomolgus islet transplant model. A marginal mass of autologous islets, that is islets prepared from 70% to 80% of the pancreas, was transplanted at 1600-4100 IEQ/kg into subtotal pancreatectomized, streptozotocin-treated and insulin-deficient diabetic hosts. In this marginal mass islet transplant model, islet function is insidiously lost over time and diabetes recurs in all untreated monkeys by 180 days posttransplantation. Short-term treatment with AAT, an acute phase reactant, in the peri-transplant period serves to terminate inflammation through effects upon expression of TGFß, NFκB and AKT and favorably altering expression of cell death and survival pathways, as detected by a system biology approach and histology. These effects enabled functional expansion of the islet mass in transplanted hosts such that graft function improves rather than deteriorating over time.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alfa 1-Antitripsina
/
Transplante das Ilhotas Pancreáticas
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Ilhotas Pancreáticas
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Diabetes Mellitus Experimental
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Rejeição de Enxerto
Limite:
Animals
Idioma:
En
Revista:
Am J Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Marrocos