Purpose: Microvesicles (MVs), 200-1000 nm bodies budding from the cell plasma membrane, are a promising source of biomarkers. This study aimed at comparing the proteome of MVs collected by ultracentrifugation from cultured Mesenchymal Stem Cells (MSCs) from Human Umbilical Cord of Preterm newborns (<34-weeks gestational age) in comparison to infants at Term (≥37 weeks). This discovery study was designed to establish the signature of prematurity. Experimental design: Orbitrap MS, statistical, bioinformatics and biochemical analyses were employed. Results: A total of 3253 proteins were identified, 78.3% matching among Preterm and Term. Principal component dimensional analyses showed that the two proteomes cluster separately. Cytoscape analysis showed that the top gene signatures cluster around inflammation and oxidative metabolism. Both Preterm and Term MVs consumed oxygen, and express ATP synthase and cytochrome oxidase, but only Preterm MVs synthesized ATP. The gene signature of Preterm condition mainly clusters around inflammation and metabolism. Conclusion and clinical relevance: MVs from MSCs conduct aerobic metabolism similarly to exosomes from the same cells, with interesting differences related to their biogenesis and function. The clinical relevance of the study lays in the perspective to utilize MVs as promising sensor of the inflammatory and metabolic state of the preterm newborn, to help in preventing the complications of prematurity.

Metabolic Signature of Microvesicles from Umbilical Cord Mesenchymal Stem Cells of Preterm and Term Infants

Ravera, Silvia;Bartolucci, Martina;Calzia, Daniela;Ramenghi, Luca A.;Panfoli, Isabella
2018

Abstract

Purpose: Microvesicles (MVs), 200-1000 nm bodies budding from the cell plasma membrane, are a promising source of biomarkers. This study aimed at comparing the proteome of MVs collected by ultracentrifugation from cultured Mesenchymal Stem Cells (MSCs) from Human Umbilical Cord of Preterm newborns (<34-weeks gestational age) in comparison to infants at Term (≥37 weeks). This discovery study was designed to establish the signature of prematurity. Experimental design: Orbitrap MS, statistical, bioinformatics and biochemical analyses were employed. Results: A total of 3253 proteins were identified, 78.3% matching among Preterm and Term. Principal component dimensional analyses showed that the two proteomes cluster separately. Cytoscape analysis showed that the top gene signatures cluster around inflammation and oxidative metabolism. Both Preterm and Term MVs consumed oxygen, and express ATP synthase and cytochrome oxidase, but only Preterm MVs synthesized ATP. The gene signature of Preterm condition mainly clusters around inflammation and metabolism. Conclusion and clinical relevance: MVs from MSCs conduct aerobic metabolism similarly to exosomes from the same cells, with interesting differences related to their biogenesis and function. The clinical relevance of the study lays in the perspective to utilize MVs as promising sensor of the inflammatory and metabolic state of the preterm newborn, to help in preventing the complications of prematurity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/890715
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