Islet Cell Laboratory
Baylor Research Institute
Circulating miroRNA 375 levels before islet autotransplantation inversely correlated with post-digestion islet yield
Morihito Takita1, Gumpei Yoshimatsu1, Mazhar A. Kanak2, Rauf Shahbazov1, Michael C. Lawrence1, Marlon F. Levy3, Bashoo Naziruddin3.
1Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, United States; 2Institute of Biomedical Studies, Baylor University, Waco, TX, United States; 3Baylor Annette C. and Harold C. Simmons Transplant Institute, Dallas, TX, United States
Background: Total pancreatectomy with islet autotransplantation (TPIAT) is the last opportunity to preserve pancreatic endocrine function for patients with intractable chronic pancreatitis whereas no biomaker has been established to predict islet isolation outcome. Circulating micro-RNA (miR) has become appreciated as diagnostic or predictive biomarker. We have shown that circulating miR-375 can be a potent biomarker for islet graft damage in clinical islet transplantation. Herein we determined if circulating miR-375 before TPIAT could be associated with islet isolation outcomes.
Methods: A total of 31 TPIAT recipients was included in this study. Islet isolation was performed with modified Ricordi methods and average yield (± S.D.) of 435 ± 266 (x 103 IEQ), accounting for 5.4 ± 3.1 (x 103 IEQ/kg of patient body weight), was transplanted into hepatic portal vein. Levels of serum C-peptide during 75g oral glucose tolerance test (OGTT) and miR375 at baseline were measured before TPIAT. Stimulated C-peptide and the difference (D) between fasting and stimulated C-peptide during OGTT were assessed for pre-surgical pancreatic endocrine function. Relative expression values of miR-375 were normalized with miR-423-3p collected from healthy subjects.
Results: Circulating miR-375 levels were significantly higher in TPIAT patients when compared to healthy subjects (n = 10, p <0.0001) (Fig. 1). Significant correlations were found between either stimulated or ∆ C-peptide during OGTT and circulating miR-375 levels at baseline in TPIAT patients (Pearson r = -0.41 or -0.40 and p = 0.02 and 0.03, respectively. Fig. 2A for ∆C-peptide); however fasting C-peptide did not achieve statistical significance in the correlation with circulating miR-375 (p = 0.18). Circulating miR-375 levels were inversely correlated with post-digestion islet yield (r = -0.37 and p = 0.04, Fig 2B) while statistical significance was lost for final islet yield after optional purification (n = 16 [52%]) (r = -0.29, p = 0.1).
Conclusions: Circulating miR-375 can be an excellent biomarker to predict pancreatic endocrine function before TPIAT and has potential to predict islet isolation outcomes. Investigation on circulating miR-375 in large-cohort of TPIAT is warranted.
This study was supported in part by Baylor Health Care System Foundation..
 Kanak MA, et al. Transplantation. 2015 Mar 12. [Epub ahead of print] DOI: 10.1097/TP.000000000000062
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|Mini-Orals: Clinical Pancreas and Islet Transplantation||Circulating miroRNA 375 levels before islet autotransplantation inversely correlated with post-digestion islet yield||Room 110|