Retrovirally transferred genes inhibit apoptosis in an insulin-secreting cell line: Implications for islet transplantation

Elizabeth S. Fenjves, M. Sofia Ochoa, Carlota Gay-Rabinstein, Camillo Ricordi, Michael A. Currant

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The transplantation of pancreatic islets for the treatment of type I diabetes is hindered by the enormous loss of cells due to early apoptotic events. Genetic engineering of islets with cytoprotective genes is an important strategy aimed to enhance the survival of these cells in the transplant setting. The present study was designed to evaluate and compare the effects of five genes on a cell line derived from insulin-producing β-cells, NIT-1. Cells were transduced using a Maloney murine leukemia virus (MLV) vector coding for yellow fluorescent protein (YFP) and for one of the following antiapoptotic genes: cFLIP, FADD-DN, BcL-2, PI-9, and ICAM-2. These genes were able to protect NIT-1 cells from cytokine-induced apoptosis to varying degrees ranging from no protection to significant protection equivalent to an optimal dose of a chemical caspase inhibitor. The data demonstrate that cFLIP, FADD-DN, and PI-9 are significantly more effective in protecting NlT-1 cells than BcL-2 and ICAM-2. Additionally, the data show that despite its weak in vitro inhibition of caspase-3, PI-9 affords significant protection against TNF-α-induced apoptosis in these cells. These genes may be ideal candidates to augment islet survival following transplantation.

Original languageEnglish
Pages (from-to)489-496
Number of pages8
JournalCell Transplantation
Volume13
Issue number5
StatePublished - Dec 8 2004

Fingerprint

Islets of Langerhans Transplantation
Insulin
Insulin-Secreting Cells
Cell death
Genes
Cells
Apoptosis
Cell Line
Genetic engineering
Transplants
Murine Leukemia Viruses
Medical problems
Caspase Inhibitors
Genetic Engineering
Viruses
Type 1 Diabetes Mellitus
Caspase 3
Proteins
Transplantation
Cytokines

Keywords

  • Apoptosis
  • Gene delivery
  • Insulinoma cell line
  • Islet transplantation
  • NIT-1

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation

Cite this

Retrovirally transferred genes inhibit apoptosis in an insulin-secreting cell line : Implications for islet transplantation. / Fenjves, Elizabeth S.; Ochoa, M. Sofia; Gay-Rabinstein, Carlota; Ricordi, Camillo; Currant, Michael A.

In: Cell Transplantation, Vol. 13, No. 5, 08.12.2004, p. 489-496.

Research output: Contribution to journalArticle

Fenjves, Elizabeth S. ; Ochoa, M. Sofia ; Gay-Rabinstein, Carlota ; Ricordi, Camillo ; Currant, Michael A. / Retrovirally transferred genes inhibit apoptosis in an insulin-secreting cell line : Implications for islet transplantation. In: Cell Transplantation. 2004 ; Vol. 13, No. 5. pp. 489-496.
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