Abstract
Plasma-derived extracellular vesicles (EV) can serve as markers of cell damage/disease but can also have therapeutic utility depending on the nature of their cargo, such as miRNA. Currently, there are challenges and lack of innovations regarding early diagnosis and therapeutic options within different aspects of management of patients suffering from chronic pancreatitis (CP). Use of EV as biomarkers for pancreatic health and/or as adjuvant therapy would make a difference in management of these patients. The aim of this study was to characterize the miRNA cargo of EV purified from the plasma of CP patients and compared to those of healthy participants. EVs were isolated from plasma of 15 CP patients and 10 healthy controls. Nanoparticle tracking analysis was used to determine frequency and size, while NanoString technology was used to characterize the miRNA cargo. Relevant clinical parameters were correlated with EV miRNA cargo. ~ 30 miRNA species were identified to have significantly (p < 0.05) different expression in EV from individuals with CP compared to healthy individuals; ~ 40 miRNA were differentially expressed in EV from pre-diabetic versus non-diabetic CP patients. miR-579-3p, while exhibiting significantly lower (~ 16-fold) expression in CP compared to healthy and lower (~ 24-fold) in CP narcotic users compared to the non-users, is actually enriched (~ 32-fold) within EV in pre-diabetic CP patients compared to non-diabetic CP patients. A unique pattern was identified in female CP patients. These data support the prospect of using a plasma-derived EV cargo to assess pancreatic health and its therapeutic potential in CP patients.
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Acknowledgements
The authors would like to thank the staff of the UNC Delta Translational Services Recharge Center and the UNC Nanomedicines Characterization Core Facility.
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This work was partly funded by NIH NIGMS T32 GM008450 (CM) and NIEHS T32 ES007126 (MW).
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Conception or design of the work: CSD, AK, RM, SMW. Data collection: MAB, MLW, CM, XB, BMW. Data analysis and interpretation: CSD, AK, RM, SMW, CM, MLW, LGC. Drafting the article: RM, CSD. Critical revision of the article: CSD, TB, SMW, AK, RM, CM.
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AK discloses a relationship with AssureImmune Cord Blood Bank and Aceso Therapeutic that includes equity.
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Desai, C.S., Khan, A., Bellio, M.A. et al. Characterization of extracellular vesicle miRNA identified in peripheral blood of chronic pancreatitis patients. Mol Cell Biochem 476, 4331–4341 (2021). https://doi.org/10.1007/s11010-021-04248-5
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DOI: https://doi.org/10.1007/s11010-021-04248-5