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Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents

Mesenchymal stem cells (MSCs) of fetal origin, such as umbilical cord blood MSCs (UCB MSCs), have emerged as a promising cell source for musculoskeletal tissue regeneration because of their higher proliferation potential, lack of donor site morbidity, and their off-the-shelf potential. MSCs differen...

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Autores principales: Klontzas, Michail E., Vernardis, Spyros I., Heliotis, Manolis, Tsiridis, Eleftherios, Mantalaris, Athanasios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439454/
https://www.ncbi.nlm.nih.gov/pubmed/28418785
http://dx.doi.org/10.1089/scd.2016.0315
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author Klontzas, Michail E.
Vernardis, Spyros I.
Heliotis, Manolis
Tsiridis, Eleftherios
Mantalaris, Athanasios
author_facet Klontzas, Michail E.
Vernardis, Spyros I.
Heliotis, Manolis
Tsiridis, Eleftherios
Mantalaris, Athanasios
author_sort Klontzas, Michail E.
collection PubMed
description Mesenchymal stem cells (MSCs) of fetal origin, such as umbilical cord blood MSCs (UCB MSCs), have emerged as a promising cell source for musculoskeletal tissue regeneration because of their higher proliferation potential, lack of donor site morbidity, and their off-the-shelf potential. MSCs differentiated toward the osteogenic lineage exhibit a specific metabolic phenotype characterized by reliance to oxidative phosphorylation for energy production and reduced glycolytic rates. Currently, limited information exists on the metabolic transitions at different stages of the osteogenic process after osteoinduction with different agents. Herein, the osteoinduction efficiency of BMP-2 and dexamethasone on UCB MSCs was assessed using gas chromatography–mass spectrometry (GC-MS) metabolomics analysis, revealing metabolic discrepancies at 7, 14, and 21 days of induction. Whereas both agents when administered individually were able to induce collagen I, osteocalcin, and osteonectin expression, BMP-2 was less effective than dexamethasone in promoting alkaline phosphatase expression. The metabolomics analysis revealed that each agent induced distinct metabolic alterations, including changes in amino acid pools, glutaminolysis, one-carbon metabolism, glycolysis, and tricarboxylic acid cycle. Importantly, we showed that in vitro-differentiated UCB MSCs acquire a metabolic physiology similar to primary osteoblasts when induced with dexamethasone but not with BMP-2, highlighting the fact that metabolomics analysis is sensitive enough to reveal potential differences in the osteogenic efficiency and can be used as a quality control assay for evaluating the osteogenic process.
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spelling pubmed-54394542017-05-30 Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents Klontzas, Michail E. Vernardis, Spyros I. Heliotis, Manolis Tsiridis, Eleftherios Mantalaris, Athanasios Stem Cells Dev Original Research Reports Mesenchymal stem cells (MSCs) of fetal origin, such as umbilical cord blood MSCs (UCB MSCs), have emerged as a promising cell source for musculoskeletal tissue regeneration because of their higher proliferation potential, lack of donor site morbidity, and their off-the-shelf potential. MSCs differentiated toward the osteogenic lineage exhibit a specific metabolic phenotype characterized by reliance to oxidative phosphorylation for energy production and reduced glycolytic rates. Currently, limited information exists on the metabolic transitions at different stages of the osteogenic process after osteoinduction with different agents. Herein, the osteoinduction efficiency of BMP-2 and dexamethasone on UCB MSCs was assessed using gas chromatography–mass spectrometry (GC-MS) metabolomics analysis, revealing metabolic discrepancies at 7, 14, and 21 days of induction. Whereas both agents when administered individually were able to induce collagen I, osteocalcin, and osteonectin expression, BMP-2 was less effective than dexamethasone in promoting alkaline phosphatase expression. The metabolomics analysis revealed that each agent induced distinct metabolic alterations, including changes in amino acid pools, glutaminolysis, one-carbon metabolism, glycolysis, and tricarboxylic acid cycle. Importantly, we showed that in vitro-differentiated UCB MSCs acquire a metabolic physiology similar to primary osteoblasts when induced with dexamethasone but not with BMP-2, highlighting the fact that metabolomics analysis is sensitive enough to reveal potential differences in the osteogenic efficiency and can be used as a quality control assay for evaluating the osteogenic process. Mary Ann Liebert, Inc. 2017-05-15 2017-05-15 /pmc/articles/PMC5439454/ /pubmed/28418785 http://dx.doi.org/10.1089/scd.2016.0315 Text en © Michail E. Klontzas et al. 2017; Published by Mary Ann Liebert, Inc. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mary Ann Liebert, Inc. offers reprint services for those who want to order professionally produced copies of articles published under the Creative Commons Attribution (CC BY) license. To obtain a price quote, email Reprints@liebertpub.com. Please include the article's title or DOI, quantity, and delivery destination in your email.
spellingShingle Original Research Reports
Klontzas, Michail E.
Vernardis, Spyros I.
Heliotis, Manolis
Tsiridis, Eleftherios
Mantalaris, Athanasios
Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents
title Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents
title_full Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents
title_fullStr Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents
title_full_unstemmed Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents
title_short Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents
title_sort metabolomics analysis of the osteogenic differentiation of umbilical cord blood mesenchymal stem cells reveals differential sensitivity to osteogenic agents
topic Original Research Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439454/
https://www.ncbi.nlm.nih.gov/pubmed/28418785
http://dx.doi.org/10.1089/scd.2016.0315
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