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 language | English |
|---|---|
| Pages (from-to) | 489-496 |
| Number of pages | 8 |
| Journal | Cell Transplantation |
| Volume | 13 |
| Issue number | 5 |
| State | Published - Dec 8 2004 |
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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 journal › Article
}
TY - JOUR
T1 - Retrovirally transferred genes inhibit apoptosis in an insulin-secreting cell line
T2 - Implications for islet transplantation
AU - Fenjves, Elizabeth S.
AU - Ochoa, M. Sofia
AU - Gay-Rabinstein, Carlota
AU - Ricordi, Camillo
AU - Currant, Michael A.
PY - 2004/12/8
Y1 - 2004/12/8
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Gene delivery
KW - Insulinoma cell line
KW - Islet transplantation
KW - NIT-1
UR - http://www.scopus.com/inward/record.url?scp=9344258616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9344258616&partnerID=8YFLogxK
M3 - Article
C2 - 15565861
AN - SCOPUS:9344258616
VL - 13
SP - 489
EP - 496
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 5
ER -