Abstract
It has been suggested that the mechanism of pancreatic β-cell death in autoimmune diabetes mellitus and in immunoisolated transplantation devices involves cytokine-induced apoptosis. To explore the feasibility of a gene transfer strategy to protect β-cells, we evaluated the use of replication defective HSV-1 amplicon vectors as gene transfer vehicles. Post-mitotic murine and human β-cells were efficiently transduced by a herpes simplex virus (HSV) vector that expresses the reporting gene Escherichia coli lacZ under the transcriptional control of a HSV promoter (HSVlac) both as islets and as single cells. Insulin secretion, a marker of β-cell function, was unaffected by HSVlac transduction of a β-cell line. A HSV amplicon vector that expressed bcl-2 (HSVbcl2) in β-cells was constructed, and its effects on cytokine-mediated apoptosis in both a β-cell line and primary murine β-cells assessed by measuring internucleosomal fragmentation. β-Cell apoptosis was blocked by transduction with HSVbcl2 but not HSVlac. The prevention of cytokine-induced apoptosis in β-cells by bcl-2 expression has the potential both to ameliorate primary autoimmune β-cell destruction as type I diabetes develops, and to prevent the destruction of transplanted β-cells inside immunoisolation devices.
Original language | English (US) |
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Pages (from-to) | 1719-1726 |
Number of pages | 8 |
Journal | Human Gene Therapy |
Volume | 7 |
Issue number | 14 |
DOIs | |
State | Published - Sep 10 1996 |
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics