Islet Viability During Transplantation

"Iron chelation may improve islet viability"

Overexpression of vascular endothelial growth factor in vitro using
deferoxamine: a new drug to increase islet vascularization during
transplantation.
Langlois A, Bietiger W, Mandes K, Maillard E, Belcourt A, Pinget M,
Kessler L, Sigrist S
Transplant Proc 2008 Mar; 40(2):473-6.

During pancreatic islet transplantation, delayed and insufficient
revascularization can deprive islets of oxygen and nutrients,
resulting in cell death and early graft failure. Deferoxamine (DFO),
an iron chelator, increases vascular endothelial growth factor (VEGF)
expression in cells. The aim of this work was to study the effect of
DFO on beta-cell and pancreatic islet viability as well as VEGF
expression. beta-cell lines from rat insulinoma (Rin m5f) and primary
cultures of pancreatic islets from Wistar rats were incubated with DFO
(10, 100, and 1000 mumol/L). The viability was evaluated using
fluorescein diacetate/propidium iodide for dying pancreatic islets and
using cell titers for Rin m5f. Expression of VEGF messenger RNA (mRNA)
was quantified using reverse transcriptase polymerase chain reaction
(RT-PCR). Finally, VEGF secretion was determined using enzyme-linked
immunosorbent assays at 1 to 3 days after treatment. The addition of
10 mumol/L of DFO preserved Rin m5F viability at 24 hours after
treatment (10 mumol/L; 101.33% +/- 5.66%; n = 7). However, 100 and
1000 mumol/L of DFO induced cell death (68.92% +/- 5.83% and 65.89%
+/- 5.83%, respectively; n = 4). In the same way, viability of
pancreatic islets in the presence of DFO was preserved. RT-PCR
analysis showed stimulation of VEGF mRNA in the presence of 10 mumol/L
of DFO in islets at 3 days after culture. Finally, 10 mumol/L of DFO
stimulated secretion of VEGF 7.95 +/- 0.84 versus 1.80 +/- 1.10 pg/mug
total protein with 10 mumol/L of DFO in rat islets at 3 days after
culture, n = 3; P < .001). The use of DFO to stimulate VEGF expression
and increase islet vascularization may be a realistic approach to
improve islet viability during transplantation.
Transplantation proceedings [Transplant Proc]
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