Your browser doesn't support javascript.
loading
Functional secretome analysis reveals Annexin-A1 as important paracrine factor derived from fetal mesenchymal stem cells in hepatic regeneration.
Zagoura, Dimitra; Trohatou, Ourania; Makridakis, Manousos; Kollia, Antonia; Kokla, Nikolitsa; Mokou, Marika; Psaraki, Adriana; Eliopoulos, Aristides G; Vlahou, Antonia; Roubelakis, Maria G.
Afiliación
  • Zagoura D; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Trohatou O; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Makridakis M; Biotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece.
  • Kollia A; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Kokla N; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Mokou M; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Biotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece.
  • Psaraki A; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • Eliopoulos AG; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Greece.
  • Vlahou A; Biotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece.
  • Roubelakis MG; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Greece. Electronic address: roubel@med.uoa.gr.
EBioMedicine ; 45: 542-552, 2019 Jul.
Article en En | MEDLINE | ID: mdl-31303498
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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A1 / Proteómica / Trasplante de Células Madre Mesenquimatosas / Regeneración Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: EBioMedicine Año: 2019 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A1 / Proteómica / Trasplante de Células Madre Mesenquimatosas / Regeneración Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: EBioMedicine Año: 2019 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Países Bajos