Gene transfection and expression of transforming growth factor-beta1 in nonobese diabetic mouse islets protects beta-cells in syngeneic islet grafts from autoimmune destruction.
Cell Transplant
; 11(6): 519-28, 2002.
Article
em En
| MEDLINE
| ID: mdl-12428741
ABSTRACT
Nonobese diabetic (NOD) mice develop diabetes and destroy syngeneic islet grafts through an autoimmune response. Because transforming growth factor (TGF)-beta1 downregulates immune responses, we tested whether overexpression of TGF-beta1 by gene transfection of NOD mouse islets could protect beta-cells in islet grafts from autoimmune destruction. NOD mouse islet cells were transfected with an adenoviral DNA expression vector encoding porcine latent TGF-beta1 (Ad TGF-beta1) or the adenoviral vector alone (control Ad vector). The frequency of total islet cells expressing TGF-beta1 protein was increased from 12 +/- 1% in control Ad vector-transfected cells to 89 +/- 4% in Ad TGF-beta1-transfected islet cells, and the frequency of beta-cells that expressed TGF-beta1 was increased from 12 +/- 1% to 60 +/- 7%. Also, secretion of TGF-beta1 was significantly increased in islets that overexpressed TGF-beta1. Ad TGF-beta1-transfected NOD mouse islets that overexpressed TGF-beta1 prevented diabetes recurrence after transplantation into diabetic NOD mice for a median of 22 days compared with only 7 days for control Ad vector-transfected islets (p = 0.001). Immunohistochemical examination of the islet grafts revealed significantly more TGF-beta1+ cells and insulin+ cells and significantly fewer CD45+ leukocytes in Ad TGF-beta1-transfected islet grafts. Also, islet beta-cell apoptosis was significantly decreased whereas apoptosis of graft-infiltrating leukocytes was significantly increased in Ad TGF-beta1-transfected islet grafts. These observations demonstrate that overexpression of TGF-beta1, by gene transfection of NOD mouse islets, protects islet beta-cells from apoptosis and autoimmune destruction and delays diabetes recurrence after islet transplantation.
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Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Transplante das Ilhotas Pancreáticas
/
Fator de Crescimento Transformador beta
/
Ilhotas Pancreáticas
Limite:
Animals
Idioma:
En
Revista:
Cell Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Canadá