First characterization of human amniotic fluid stem cell extracellular vesicles as a powerful paracrine tool endowed with regenerative potential

Andrea Papait, Andrea Papait, Carolina Balbi, Martina Piccoli, Lucio Barile, Andrea Armirotti, Elisa Principi, Daniele Reverberi, Luisa Pascucci, Pamela Becherini, Luigi Varesio, Massimo Mogni, Domenico Coviello, Tiziano Bandiera, Michela Pozzobon, Ranieri Cancedda, Sveva Bollini

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Human amniotic fluid stem cells (hAFS) have shown a distinct secretory profile and significant regenerative potential in several preclinical models of disease. Nevertheless, little is known about the detailed characterization of their secretome. Herein we show for the first time that hAFS actively release extracellular vesicles (EV) endowed with significant paracrine potential and regenerative effect. c-KIT+ hAFS were isolated from leftover samples of amniotic fluid from prenatal screening and stimulated to enhance EV release (24 hours 20% O2 versus 1% O2 preconditioning). The capacity of the c-KIT+ hAFS-derived EV (hAFS-EV) to induce proliferation, survival, immunomodulation, and angiogenesis were investigated in vitro and in vivo. The hAFS-EV regenerative potential was also assessed in a model of skeletal muscle atrophy (HSA-Cre, SmnF7/F7 mice), in which mouse AFS transplantation was previously shown to enhance muscle strength and survival. hAFS secreted EV ranged from 50 up to 1,000 nm in size. In vitro analysis defined their role as biological mediators of regenerative, paracrine effects while their modulatory role in decreasing skeletal muscle inflammation in vivo was shown for the first time. Hypoxic preconditioning significantly induced the enrichment of exosomes endowed with regenerative microRNAs within the hAFS-EV. In conclusion, this is the first study showing that c-KIT+ hAFS dynamically release EV endowed with remarkable paracrine potential, thus representing an appealing tool for future regenerative therapy.
Lingua originaleEnglish
pagine (da-a)1340-1355
Numero di pagine16
RivistaStem cells translational medicine
Volume6
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Amniotic Fluid
  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Proliferation
  • Exosomes
  • Extracellular Vesicles
  • Extracellular vesicles
  • Fetal stem cells
  • Humans
  • Male
  • MiRNA
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs
  • Muscle, Skeletal
  • Muscular Atrophy
  • Paracrine communication
  • Proliferation
  • Stem Cell Transplantation
  • Stem Cells
  • Tissue regeneration

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