title: Evaluation of MicroRNA375 as a Novel Biomarker for Graft Damage in Clinical Islet Transplantation.
abstract: BACKGROUND
  Early and sensitive detection of islet graft damage is essential for improving posttransplant outcomes. MicroRNA 375 (miR375) has been reported as a biomarker of pancreatic β-cell death in small animal models.
  
  
  METHODS
  The miR375 levels were measured in purified human islets, sera from patients with autologous and allogeneic islet transplantation as well as total pancreatectomy alone (nontransplanted group). The miR375 levels were also determined in a miniaturized in vitro tube model comprising human islets and autologous blood.
  
  
  RESULTS
  The miR375 expression level in islets was dose-dependent (P < 0.001) and significantly elevated after islet damage in plasma in the in vitro model (P = 0.003). Clinical analysis revealed that circulating miR375 levels in both autologous and allogeneic islet recipients were significantly elevated for 7 days after islet infusion, compared with the nontransplanted group (P = 0.005 and <0.001, respectively). Furthermore, miR375 detected the difference in islet graft damage among 3 different anti-inflammatory protocols for clinical autologous transplantation (P < 0.01).
  
  
  CONCLUSIONS
  Circulating miR375 can be a reliable biomarker to detect graft damage in clinical islet transplantation because serum C-peptide and proinsulin levels are difficult to interpret due to the influence of multiple factors, such as β-cell stress and physiological response.
authors.affiliation: 1 Institute of Biomedical Studies, Baylor University, Waco, TX. 2 Islet Cell Laboratory, Baylor Research Institute, Dallas, TX. 3 Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester, UK. 4 Baylor Annette C. and Harold C. Simmons Transplant Institute, Dallas, TX.
authors.forename: Mazhar A
authors.initials: MA
authors.lastname: Kanak
authors.forename: Morihito
authors.initials: M
authors.lastname: Takita
authors.forename: Rauf
authors.initials: R
authors.lastname: Shahbazov
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lawrence
authors.forename: Wen Yuan
authors.initials: WY
authors.lastname: Chung
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Dennison
authors.forename: Marlon F
authors.initials: MF
authors.lastname: Levy
authors.forename: Bashoo
authors.initials: B
authors.lastname: Naziruddin
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D005819:Genetic Markers; C540933:MIRN375 microRNA, human; D035683:MicroRNAs