Retrovirally Transferred Genes Inhibit Apoptosis in an Insulin-Secreting Cell Line: Implications for Islet Transplantation

• Main Authors: Elizabeth S. Fenjves, M. Sofia Ochoa, Carlota Gay-Rabinstein, Camillo Ricordi, Michael A. Curran
• Format: Article
• Language: English
• Published: SAGE Publishing 2004-07-01
• Series: Cell Transplantation
• Online Access: https://doi.org/10.3727/000000004783983710

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 NIT-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.