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

Bruschi, Maurizio; Santucci, Laura; Ravera, Silvia; Bartolucci, Martina; Petretto, Andrea; Calzia, Daniela; Ramenghi, Luca A.; Candiano, Giovanni; Panfoli, Isabella

doi:10.1002/prca.201700082

Cited by 32 publications

(32 citation statements)

References 37 publications

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“…Otherwise, for example, the mitochondrial superoxide dismutase would have been highlighted. This is consistent with the hypothesis that the oxidative damage may derive from an OxPhos dysfunction both inside the mitochondria and in ectopic locations, that has been reported in plasma membranes, 41‐45 myelin sheath, rod disks, exosomes, and MV 17,46‐48 . The expression of mitochondrial components of the electron transfer chain (ETC) and F o F 1 ‐ATP synthase in ectopic sites not protected by a double membrane poses greater risks for oxidative stress generation and implies the involvement of GSS.…”

Section: Discussionsupporting

confidence: 90%

“…Inflammation, hyperoxia, and ischemia challenge the newborn, and free radical‐induced oxidative stress production is almost a paradigm of prematurity 15,16 . In fact, antioxidant defense mechanisms are incompletely developed in preterm newborns 16‐18 . Our ELISA test on newborn serum showed that the elevated levels of reactive oxygen species (ROS) in the preterm were reduced in the treated preterm cohort.…”

Section: Discussionmentioning

confidence: 90%

“…The present work explored the effect of dietary n‐3 PUFA supplementation of pregnant women diagnosed with threatened preterm delivery on their offspring. MV from cord blood were utilized, as our previous data 17 suggest that, differently from exosomes, MV are good predictors of the overall bioenergetic status of the organism from which they come from, as they derive from the plasma membrane 17 …”

Section: Discussionmentioning

confidence: 99%

“…Their surface and luminal cargo plays a role in health and disease, and is a promising source of biomarkers 16 . We have previously shown that MV from umbilical cord mesenchymal stem cells bear an interesting metabolic signature 17 . MV may be regarded as sensors of the inflammatory and metabolic and inflammatory status of the individual 16,17 …”

Section: Introductionmentioning

confidence: 99%

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Association between maternal omega‐3 polyunsaturated fatty acids supplementation and preterm delivery: A proteomic study

et al. 2020

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Maternal nutrition during pregnancy influences offspring health. Dietary supplementation of pregnant women with (n-3) long-chain polyunsaturated fatty acids (PUFA) was shown to exert beneficial effects on offspring, through yet unknown mechanisms. Here, we conducted a dietary intervention study on a cohort of 10 women diagnosed with threatened preterm labor with a nutritional integration with eicosapentaenoic and docosahexaenoic acids. Microvesicles (MV) isolated form arterial cord blood of the treated cohort offspring and also of a randomized selection of 10 untreated preterm and 12 term newborns, were characterized by dynamic light scattering and analyzed by proteomic and statistical analysis. Glutathione synthetase was the protein bearing the highest discrimination ability between cohorts. ELISA assay showed that glutathione synthetase was more abundant in cord blood from untreated preterm compared to the other conditions. Assay of free SH-groups showed that serum of preterm subjects was oxidized. Data suggest that preterm suffer from oxidative stress, which was lower in the treated cohort. This study confirms that MV are a representative sample of the individual status and the efficacy of dietary intervention with PUFA in human pregnancy in terms of lowered inflammatory status, increased gestational age and weight at birth. K E Y W O R D Sdocosahexaenoic acids, eicosapentaenoic acids, glutathione synthetase, microvesicles, premature birth | 6323 BRUSCHI et al.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between maternal omega‐3 polyunsaturated fatty acids supplementation and preterm delivery: A proteomic study

et al. 2020

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“…Importantly, FZD2 is the receptor of Wnt5a/b and FZD2 mutations in uence Wnt signaling, which mediates the epithelial to mesenchymal transition (EMT) during lung development [50]. In addition, by comparing the proteome of microvesicles collected from hUC-MSC CM between preterm and term groups, Bruschi et al found that 173 proteins were signi cantly changed, 163 of which were increased in the preterm group [51]. However, there have been no comprehensive comparisons of hUC-MSC CM peptidomic pro les between preterm and term infants.…”

Section: Discussionmentioning

confidence: 99%

Peptidome Analysis of Umbilical Cord Mesenchymal Stem Cell (hUC-MSC) Conditioned Medium from Preterm and Term Infants

Wang

Zhang

et al. 2020

Preprint

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Background: The therapeutic role of mesenchymal stem cells (MSCs) has been widely confirmed in several animal models of premature infant diseases. Micromolecule peptides have shown promise for the treatment of premature infant diseases. However, the potential role of peptides secreted from MSCs has not been studied. The purpose of this study is to helps to broaden the knowledge of the hUC-MSC secretome at the peptide level through peptidomic profile analysis.Methods: We used tandem mass tag (TMT) labeling technology followed by tandem mass spectrometry to compare the peptidomic profile of preterm and term umbilical cord MSC (hUC-MSC) conditioned medium (CM). Gene Ontology (GO) enrichment analysis and Ingenuity Pathway Analysis (IPA) were conducted to explore the differentially expressed peptides by predicting the functions of their precursor proteins. To evaluate the effect of candidate peptides on human lung epithelial cells stimulated by hydrogen peroxide (H2O2), quantitative real-time PCR (qRT-PCR), western blot analysis and enzyme-linked immunosorbent assay (ELISA) were respectively adopted to detect inflammatory cytokines (TNF-α, IL-1β and IL-6) expression levels at the mRNA and protein levels,Results: A total of 131 peptides derived from 106 precursor proteins were differentially expressed in the preterm hUC-MSC CM compared with the term group, comprising 37 up-regulated peptides and 94 down-regulated peptides. Bioinformatics analysis showed that these differentially expressed peptides may be associated with developmental disorders, inflammatory response and organismal injury. We also found that peptides 7118TGAKIKLVGT7127 derived from MUC19 and 508AAAAGPANVH517 derived from SIX5 reduced the expression levels of TNF-α, IL-1β and IL-6 in H2O2-treated human lung epithelial cells.Conclusions: In summary, this study provides further secretomics information on hUC-MSCs and provides a series of peptides that might have antiinflammatory effects on pulmonary epithelial cells and contribute to the prevention and treatment of respiratory diseases in premature infants.

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Proteomic profiling of mesenchymal stem cell‐derived extracellular vesicles: Impact of isolation methods on protein cargo

Abyadeh,

Mirshahvaladi,

Kashani

et al. 2024

J of Extracellular Bio

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Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are secreted by cells and play a critical role in cell‐to‐cell communication. Despite the promising reports regarding their diagnostic and therapeutic potential, the utilization of EVs in the clinical setting is limited due to insufficient information about their cargo and a lack of standardization in isolation and analysis methods. Considering protein cargos in EVs as key contributors to their therapeutic potency, we conducted a tandem mass tag (TMT) quantitative proteomics analysis of three subpopulations of mesenchymal stem cell (MSC)‐derived EVs obtained through three different isolation techniques: ultracentrifugation (UC), high‐speed centrifugation (HS), and ultracentrifugation on sucrose cushion (SU). Subsequently, we checked EV marker expression, size distribution, and morphological characterization, followed by bioinformatic analysis. The bioinformatic analysis of the proteome results revealed that these subpopulations exhibit distinct molecular and functional characteristics. The choice of isolation method impacts the proteome of isolated EVs by isolating different subpopulations of EVs. Specifically, EVs isolated through the high‐speed centrifugation (HS) method exhibited a higher abundance of ribosomal and mitochondrial proteins. Functional apoptosis assays comparing isolated mitochondria with EVs isolated through different methods revealed that HS‐EVs, but not other EVs, induced early apoptosis in cancer cells. On the other hand, EVs isolated using the sucrose cushion (SU) and ultracentrifugation (UC) methods demonstrated a higher abundance of proteins primarily involved in the immune response, cell‐cell interactions and extracellular matrix interactions. Our analyses unveil notable disparities in proteins and associated biological functions among EV subpopulations, underscoring the importance of meticulously selecting isolation methods and resultant EV subpopulations based on the intended application.

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

Cited by 32 publications

References 37 publications

Association between maternal omega‐3 polyunsaturated fatty acids supplementation and preterm delivery: A proteomic study

Association between maternal omega‐3 polyunsaturated fatty acids supplementation and preterm delivery: A proteomic study

Peptidome Analysis of Umbilical Cord Mesenchymal Stem Cell (hUC-MSC) Conditioned Medium from Preterm and Term Infants

Proteomic profiling of mesenchymal stem cell‐derived extracellular vesicles: Impact of isolation methods on protein cargo

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