Exosomes Carry Stress and Damage Specific miRNAs during Peritransplant Period in TPIAT
1Department of Surgery, Virginia Commonwealth University, VCU Health, Richmond, VA, 2Islet Cell Lab, Baylor Scott and White Research Institute, Dallas, TX, 3Simmons Transplant Institute, Baylor Scott and White Medical Center, Dallas, TX
Meeting: 2019 American Transplant Congress
Abstract number: A127
Keywords: Graft function, Islets, Outcome, Pancreatitis
Session Information
Date: Saturday, June 1, 2019
Session Name: Poster Session A: Islet Cell and Cell Transplantation
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Innate inflammation and hypoxia during peritransplant period significantly affect survival of islet grafts. Markers that can identify stress and/or damage during this early period may improve transplant outcomes. Exosomes are nano-sized, extracellular vesicles that carry information pertaining to the cells health. Pancreatic islets exposed to cytokines and/or hypoxia release exosomes that carry miRNAs that may be differentially regulated. In this study, we measured the exosomal miRNAs released by stressed or damaged islets during peri-transplant period and its significance with 1 year post transplant outcomes in TPIAT cases
*Methods: Purified human islets were subjected to hypoxia and pro-inflammatory cytokines for 24 hrs to induce stress. Islet exosomes were isolated and miRNAs were sequenced using Illumina Nex-gen sequencing. The data was further validated using LNA based qPCR assays. Finally, the stress related exo-miRNAs were measured in the plasma samples collected during the peritransplant period in TPIAT cases (n=6) and the data was correlated with 1 year post transplant c-peptide, SUITO index and HbA1c.
*Results: Global exo-miRNA sequencing revealed 879 miRNA species were released from intact human islets and 170 exo-miRNAs were differentially expressed in response to stress. Exo-miRNAs 29b-3p and 216a-5p were significantly upregulated within 6 h of exposure to cytokines and hypoxia mediated stress whereas, miR 148a-3p and miR-375 were upregulated at 24-48 h, correlating with apoptotic damage. In TPIAT patients, stress and damage associated exo-miRNAs were significantly elevated in circulation during peritransplant period and also, negatively correlated with 1 year post-transplant SUITO index (p=0.019, n=6). There was no significant correlation between peritransplant exo-miRNAs with c-peptide (p=0.460, n=6), and HbA1c (p<0.069, n=6).
*Conclusions: Overall, we have identified a novel set of exosomal miRNAs that are released by islets in response to peritransplant inflammatory and hypoxic stress. These findings may have clinical implications by monitoring stressed islets and introduce appropriate interventions during islet transplantation to improve the graft outcome.
To cite this abstract in AMA style:
Saravanan P, Kanak M, Vasu S, Lawrence M, Levy M, Naziruddin B. Exosomes Carry Stress and Damage Specific miRNAs during Peritransplant Period in TPIAT [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/exosomes-carry-stress-and-damage-specific-mirnas-during-peritransplant-period-in-tpiat/. Accessed December 12, 2019.« Back to 2019 American Transplant Congress