title: Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.
abstract: Exosomes are secreted nanovesicles that are able to transfer RNA and proteins to target cells. The emerging role of mesenchymal stem cell (MSC) exosomes as promoters of aerobic ATP synthesis restoration in damaged cells, prompted us to assess whether they contain an extramitochondrial aerobic respiration capacity. Exosomes were isolated from culture medium of human MSCs from umbilical cord of ≥37-wk-old newborns or between 28- to 30-wk-old newborns (i.e.,term or preterm infants). Characterization of samples was conducted by cytofluorometry. Oxidative phosphorylation capacity was assessed by Western blot analysis, oximetry, and luminometric and fluorometric analyses. MSC exosomes express functional respiratory complexes I, IV, and V, consuming oxygen. ATP synthesis was only detectable in exosomes from term newborns, suggestive of a specific mechanism that is not completed at an early gestational age. Activities are outward facing and comparable to those detected in mitochondria isolated from term MSCs. MSC exosomes display an unsuspected aerobic respiratory ability independent of whole mitochondria. This may be relevant for their ability to rescue cell bioenergetics. The differential oxidative metabolism of pretermvs.term exosomes sheds new light on the preterm newborn's clinical vulnerability. A reduced ability to repair damaged tissue and an increased capability to cope with anoxic environment for preterm infants can be envisaged.-Panfoli, I., Ravera, S., Podestà, M., Cossu, C., Santucci, L., Bartolucci, M., Bruschi, M., Calzia, D., Sabatini, F., Bruschettini, M., Ramenghi, L. A., Romantsik, O., Marimpietri, D., Pistoia, V., Ghiggeri, G., Frassoni, F., Candiano, G. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Panfoli
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy silvia.ravera@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ravera
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Podestà
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cossu
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Santucci
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Bartolucci
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Calzia
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sabatini
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bruschettini
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Luca Antonio
authors.initials: LA
authors.lastname: Ramenghi
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Romantsik
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Marimpietri
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Ghiggeri
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.affiliation: *Dipartimento di Farmacia, Laboratorio di Biochimica, Università di Genova, Genoa, Italy; and Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Laboratory of Pathophysiology of Uremia, Neonatal Intensive Care Unit, and Laboratorio Oncologia, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D015153:Blotting, Western; D002478:Cells, Cultured; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010092:Oximetry; D010101:Oxygen Consumption; D047929:Term Birth / Q000097:blood / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I
keywords: ATP synthesis; electron transport chain; energy metabolism; oxidative phosphorylation; umbilical cord