Background: Pancreatic islets with high quality are essential for better endocrine function and post-transplant outcome in total pancreatectomy with islet autotransplantation (TPIAT). The islets are subjected to stress throughout the isolation process that account for considerable variation in quality and yield. Earlier, we have demonstrated that miR-375 is highly a sensitive and reliable marker for islet cell damage in transplant recipients. Here we examined islet-enriched miRNAs 375 and 200c released during various isolation steps to assess damage and correlated the findings for significance with post-transplant islet graft function.

Methods: The absolute concentration of miR-375, miR-200c and C-peptide were measured in various islet isolation steps including digestion, dilution, recombination, purification and bagging steps during TPIAT (n=12) using qPCR and ELISA. After transplantation, glycemic control in patients was monitored using C-peptide, HbA1c, insulin requirement and SUITO index.

Results: The amount of miR-375 released during the initial stages of pancreas digestion is significantly higher than other steps (P < 0.001). MiR-375 profiles among isolation steps were bimodal with higher peaks observed during pancreatic digestion and bagging than during islet purification or recombination (206.92 ± 196.74 vs 48.06 ± 71.90 vs 1.88 ± 3.32 fmol). MiR-200c also mirrored these changes albeit with 10⁴ less concentration. In contrast, the C-peptide amount is significantly higher in the purification and bagging compared to the other steps (P < 0.001). Lower miR-375 released during digestion ((AUC) _D /g < 20 fmol) is significantly associated with lower post-transplant insulin requirement in patients at 6 months (p=0.03), HbA1c (p=0.04) when compared to higher release of miR-375 ((AUC) _D/g > 20) fmol. Similarly, higher C-peptide and SUITO index were observed at 6 month post-transplant in the lower miR-375 release group.

Conclusion: Measurement of absolute quantity of miRNAs 375 and 200c released during islet isolation is a useful tool to accurately assess islet damage. Furthermore, total miRNA release is indicative of the post-transplant endocrine function in TPIAT patients.

CITATION INFORMATION: Saravanan P, Kanak M, Yoshimatsu G, Lawrence M, Naziruddin B. Assessment of Islet Damage During Isolation Utilizing miRNAs and Its Significance with Post-Transplant Outcome in TPIAT. Am J Transplant. 2017;17 (suppl 3).

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