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Cited by 39Mesenchymal stem cell researchLiver physiology and pathologyTissue Engineering and Regenerative Medicine

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Functional secretome analysis reveals Annexin-A1 as important paracrine factor derived from fetal mesenchymal stem cells in hepatic regeneration

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Zagoura, Dimitra, Trohatou, Ourania, Makridakis, Manousos, Kollia, Antonia, Kokla, Nikolitsa, Mokou, Marika, Psaraki, Adriana, Eliopoulos, Aristides G., Vlahou, Antonia, Roubelakis, Maria G.·2019·EBioMedicine
DOI 10.1016/j.ebiom.2019.07.009PMC PMC6642415
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Abstract

BACKGROUND: Human mesenchymal stem/stromal cells (MSCs) and their secreted molecules exert beneficial effects in injured tissues by promoting tissue regeneration and angiogenesis and by inhibiting inflammation and fibrosis. We have previously demonstrated that the therapeutic activity of fetal MSCs derived from amniotic fluid (AF-MSCs) and their hepatic progenitor-like cells (HPL) is mediated by paracrine effects in a mouse model of acute hepatic failure (AHF). METHODS: Herein, we have combined proteomic profiling of the AF-MSCs and HPL cell secretome with ex vivo and in vivo functional studies to identify specific soluble factors, which underpin tissue regeneration in AHF. FINDINGS: The anti-inflammatory molecule Annexin-A1 (ANXA1) was detected at high levels in both AF-MSC and HPL cell secretome. Further functional analyses revealed that the shRNA-mediated knock-down of ANXA1 in MSCs (shANXA1-MSCs) decreased their proliferative, clonogenic and migratory potential, as well as their ability to differentiate into HPL cells. Liver progenitors (oval cells) from AHF mice displayed reduced proliferation when cultured ex vivo in the presence of conditioned media from shANXA1-MSCs compared to control MSCs secretome. Intra-hepatic delivery of conditioned media from control MSCs but not shANXA1-MSCs reduced liver damage and circulating levels of pro-inflammatory cytokines in AHF. INTERPRETATION: Collectively, our study uncovers secreted Annexin-A1 as a novel effector of MSCs in liver regeneration and further underscores the potential of cell-free therapeutic strategies for liver diseases. FUND: Fondation Santé, GILEAD Asklipeios Grant, Fellowships of Excellence - Siemens, IKY, Reinforcement of Postdoctoral Researchers, IKY.

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  • ANXA1 present in amniotic fluid-derived MSC-secretome ameliorates liver damage in a CCl4-induced liver injury mouse model by inducing hepatic progenitor proliferation, migration and differentiation while reducing inflammation.

    “In addition, the anti‑inflammatory molecule annexin-A1 (ANXA1) present in amniotic fluid-derived MSC-secretome ameliorated liver damage in a CCl4‑induced liver injury mouse model by inducing hepatic progenitor proliferation, migration and differentiation while reducing inflammation [195].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [195]

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Metadata

Authors
Zagoura, D., Trohatou, O., Makridakis, M., Kollia, A., Kokla, N., Mokou, M., Psaraki, A., Eliopoulos, A. G., Vlahou, A., & Roubelakis, M. G.
Affiliations
  • National and Kapodistrian University of Athens (GR)
  • Biomedical Research Foundation of the Academy of Athens (GR)
Corresponding author
Roubelakis, Maria G.
ORCID
Venue
EBioMedicine
Publisher
Elsevier BV
Published
2019-07
Volume
45
Pages
542-552
ISSN
2352-3964 (ISSN-L)
DOI
10.1016/j.ebiom.2019.07.009
PMC
PMC6642415
OpenAlex
W2960796576
Cited by
39
References
2
Citations by year
2026: 3 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 1
FWCI
3.43
Type
journal article
Language
en
Open access
Licence
Locations
  • EBioMedicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Siemens Foundation
  • European Commission
  • European Social Fund (MIS-5001552)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
annexin A1, mesenchymal stem cells, amniotic fluid stem cells, secretome, paracrine signaling, acute liver failure, liver regeneration, anti-inflammatory cytokines, cell-free therapy, oval cells, stem cell differentiation
MeSH terms
Animals, Bone Marrow Cells, Fetus, Humans, Liver, Liver Regeneration, Culture Media, Conditioned, Annexin A1, Intercellular Signaling Peptides and Proteins, Proteomics, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Mice, Mesenchymal Stem Cells

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