Circulating Endothelial Progenitor Cells Present an Inflammatory Phenotype and Function in Patients With Alcoholic Liver Cirrhosis

Endothelial progenitor cells (EPCs) have been implicated in liver injury and repair. However, the phenotype and potential of these heterogenous EPCs remain elusive. In particular, their involvement in the pathogenesis of alcoholic liver cirrhosis (ALC) remains unclear. The current study extensively...

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Published inFrontiers in physiology Vol. 9; p. 556
Main Authors Kaur, Savneet, Sehgal, Rashi, Shastry, Saggere M, McCaughan, Geoffrey, McGuire, Helen M, Fazekas St de Groth, Barbara, Sarin, Shiv, Trehanpati, Nirupma, Seth, Devanshi
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 22.05.2018
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Summary:Endothelial progenitor cells (EPCs) have been implicated in liver injury and repair. However, the phenotype and potential of these heterogenous EPCs remain elusive. In particular, their involvement in the pathogenesis of alcoholic liver cirrhosis (ALC) remains unclear. The current study extensively characterized the phenotype and functions of EPCs to understand their role in ALC pathogenesis. Circulating EPCs were identified as CD34+CD133+CD31+ cells by flow cytometer in ALC patients ( = 7) and healthy controls (HC, = 7). A comprehensive characterization of circulating EPCs using more than 30 phenotype markers was performed by mass cytometer time of flight (CyTOF) in an independent cohort of age and gender matched ALC patients ( = 4) and controls ( = 5). cultures of circulating EPCs from ALC patients ( = 20) and controls ( = 18) were also tested for their functions, including colony formation, LDL uptake, lectin binding and cytokine secretion (ELISA). Three distinct populations of circulating EPCs (CD34+CD133+CD31+) were identified, classified on their CD45 expression (negative: CD45 ; intermediate: CD45 ; high: CD45 ). CD45 and CD45 EPCs significantly increased in ALC patients compared to controls ( -val = 0.006). CyTOF data showed that CD45 EPCs were distinct from CD45 and CD45 EPCs, with higher expression of T cell and myeloid markers, including CD3, CD4, HLA-DR, and chemokine receptors, CCR2, CCR5, CCR7, and CX3CR1. Similar to circulating EPCs, percentage of CD45 CD34+CD31+ EPCs in cultures from patients, were significantly higher compared to controls ( < 0.05). Cultured EPCs from patients also showed increased LDL uptake, lectin binding and release of TNF-alpha, RANTES, FGF-2, and VEGF. We report the first extensive characterization of circulating human EPCs with distinct EPC subtypes. Increase in CD45 EPC subtype in ALC patients with enhanced functions, inflammatory cytokines and angiogenic mediators in patients suggests an inflammatory role for these cells in ALC.
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This article was submitted to Gastrointestinal Sciences, a section of the journal Frontiers in Physiology
Edited by: Atsushi Masamune, Tohoku University, Japan
These authors have contributed equally to this work.
Reviewed by: Takayuki Kogure, Tohoku Medical and Pharmaceutical University, Japan; Michael Hickey, Monash University, Australia
ISSN:1664-042X
1664-042X
DOI:10.3389/fphys.2018.00556