Reversal of diabetes in mice by implantation of human fibroblasts genetically engineered to release mature human insulin
Articolo
Data di Pubblicazione:
1999
Citazione:
Reversal of diabetes in mice by implantation of human fibroblasts genetically engineered to release mature human insulin / L. Falqui, S. Martinenghi, G.M. Severini, P. Corbella, M.V Taglietti, C. Arcelloni, E. Sarugeri, L.D Monti, R. Paroni, N. Dozio, G. Pozza, C. Bordignon. - In: HUMAN GENE THERAPY. - ISSN 1043-0342. - 10:11(1999 Jul 20), pp. 1753-1762.
Abstract:
Autoimmune destruction of pancreatic B cells in type I, insulin-dependent diabetes mellitus (IDDM) results
in the loss of endogenous insulin secretion, which is incompletely replaced by exogenous insulin administration.
The functional restoration provided by allogeneic B-cell transplantation is limited by adverse effects of
immunosuppression. To pursue an insulin replacement therapy based on autologous, engineered human non-
B cells, we generated a retroviral vector encoding a genetically modified human proinsulin, cleavable to insulin
in non-B cells, and a human nonfunctional cell surface marker. Here we report that this vector efficiently
transduced primary human cells, inducing the synthesis of a modified proinsulin that was processed
and released as mature insulin. This retrovirally derived insulin displayed in vitro biological activity, specifically
binding to and phosphorylation of the insulin receptor, comparable to human insulin. In vivo, the transplantation
of insulin-producing fibroblasts reverted hyperglycemia in a murine model of diabetes, whereas
proinsulin-producing cells were ineffective. These results support the possibility of developing insulin production
machinery in human non-B cells for gene therapy of IDDNI.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Insulin-dependent diabetes mellitus (IDDM); Capillary electrophoresis; Gene therapy.
Elenco autori:
L. Falqui, S. Martinenghi, G.M. Severini, P. Corbella, M.V Taglietti, C. Arcelloni, E. Sarugeri, L.D Monti, R. Paroni, N. Dozio, G. Pozza, C. Bordignon
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