ESOT 2011 Report – Are young donors suitable for Islet donation?

Donor variables have a significant impact on the outcome of islet isolation. Importantly, young donor age has in the past been negatively associated with islet isolation yield. The aim of this study was to identify the outcomes of islet isolation from donors who were less than 20 years of age and to compare the results with donor population as a whole.

Ismail Sert, and colleagues from the Geneva University Hospital, Geneva, Switzerland retrospectively analyzed 432 pancreas isolations performed from brain death donors between 2002 and 2010. The pancreases preserved using the two–layer method were excluded from the analysis. The researchers reviewed 23 donor charts from donors younger than 20 years of age and their islet isolation outcomes, and compared them with our whole donor pool. An identical enzymatic isolation procedure was used for donors less than and over 20 years of age.

The results presented showed that the median age, BMI and cold ischaemia time were 17.7±3, 23.1±4.6, 372±129 min, respectively. Average digestion time was 16±4 min. For two pancreases, isolation couldn’t be performed due to technical failure. The mean islet recovery for 21 donors and transplanted preparations were 197±142 x 10³ IEQ, 326±82 × 10³ IEQ, respectively. The islet isolation success rate (transplanted islet preparations and yield >250 × 10³ IEQ) was 9/23 (39%). For the whole donor pool and transplanted preparations, mean islet yields were 252±125 × 10³ IEQ, 341±97 × 10³ IEQ, respectively and rate of transplanted preparations was 122/307 (39.7%)

The researchers concluded that despite previous reports on the negative impact of age on islet yield in this study it was not shown. In spite of the known difficulties in extracting islets from pancreas from donors less than 20 years of age, there was no difference in the transplant rates and islet yield for transplanted preparations between young donors and whole donor pool.

 

Following on the theme of islet loss Sophie Borot presented data on the quantification of islet loss during immune rejection. She explained that monitoring the fate of transplanted islets remains a major challenge in clinical islet transplantation (IT).

Sophie Borort and colleagues from Switzerland and Germany developed a MRI imaging protocol (3D difference ultra-short echo-time [dUTE]), resulting in positive contrast images of superparamagnetic iron-oxide (SPIO) nanoparticles-labeled islets transplanted in rats. The aim of the study was to compare the evolution of the MRI signal in 3 types of IT in the rat model.

The researchers used syngenic and allogeneic SPIO-labeled islets (ferucarbotran, 280μg/ml iron) that were injected intraportally into streptozotocin-induced diabetic Lewis rats. Xenogenic human islets were transplanted into normoglycaemic rats and graft functionality was evaluated by serum human C-peptide levels. Images were performed on a 3T MRI, from day 0 up to day 106. An intensity threshold was applied within the liver region, giving automatically the number of dUTE-enhanced pixels, allowing quantification. Histological studies included insulin, CD4 and CD8 staining and iron detection.

The results of the study showed that decay rates for the 3 types of IT were different.

The syngenic graft signal showed a 20% decrease during the first 2 weeks and remained stable up thereafter. For allogenic transplantation, islet rejection (G>20mmol/l) occurred at day 7.7±0.5 and 41%±12 of the initial signal was lost. In the xenogenic model, 43%±8 of the initial signal was lost by day 3, when significant basal and stimulated human C-peptide levels were not detected any longer. Islet rejection was confirmed by islet CD4+ and CD8+ cell infiltration and loss of insulin staining.

The researchers concluded thatafter intra-portal IT and during immune rejection, the loss of SPIO-labelled islets can be monitored with clinical-grade 3T MRI imaging using a semi-automatic quantification method. The decay of the signal is correlated with the graft function and histological findings.

References:

RO-172 – ARE YOUNG DONORS SUITABLE FOR ISLET ISOLATION? Ismail Sert et al. Geneva, Switzerland

RO-173 – QUANTIFICATION OF ISLET LOSS DURING IMMUNE REJECTION USING IRON-LABELED ISLET CELLS BY 3T MRI IN THE RAT MODEL. Sophie Borot et al. Geneva, Switzerland and Erlangen, Germany