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Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons

Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consum...

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Autores principales: Gorsky, Anna, Monsour, Molly, Nguyen, Hung, Castelli, Vanessa, Lee, Jea-Young, Borlongan, Cesar V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10025198/
https://www.ncbi.nlm.nih.gov/pubmed/35857254
http://dx.doi.org/10.1007/s12017-022-08720-3
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author Gorsky, Anna
Monsour, Molly
Nguyen, Hung
Castelli, Vanessa
Lee, Jea-Young
Borlongan, Cesar V.
author_facet Gorsky, Anna
Monsour, Molly
Nguyen, Hung
Castelli, Vanessa
Lee, Jea-Young
Borlongan, Cesar V.
author_sort Gorsky, Anna
collection PubMed
description Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consumption rates using the Seahorse technology. Subsequently, primary neurons were subjected to oxygen glucose deprivation (OGD) and then co-cultured with either nMSCs or sMSCs. Compared to nMSCs, sMSCs displayed higher basal energy production, larger spare respiratory capacity, greater ATP production, and decreased proton leak. Co-culture of OGD-exposed neurons with sMSCs conferred greater cell viability, enhanced cell metabolism, reduced mitochondrial reactive oxidative species mRNA, and elevated mitochondria ATP mRNA than those cultured with nMSCs. Metabolic switching produces “super” mitochondria that may underlie the therapeutic benefit of using sMSCs to treat ischemic cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12017-022-08720-3.
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spelling pubmed-100251982023-03-21 Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons Gorsky, Anna Monsour, Molly Nguyen, Hung Castelli, Vanessa Lee, Jea-Young Borlongan, Cesar V. Neuromolecular Med Research Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consumption rates using the Seahorse technology. Subsequently, primary neurons were subjected to oxygen glucose deprivation (OGD) and then co-cultured with either nMSCs or sMSCs. Compared to nMSCs, sMSCs displayed higher basal energy production, larger spare respiratory capacity, greater ATP production, and decreased proton leak. Co-culture of OGD-exposed neurons with sMSCs conferred greater cell viability, enhanced cell metabolism, reduced mitochondrial reactive oxidative species mRNA, and elevated mitochondria ATP mRNA than those cultured with nMSCs. Metabolic switching produces “super” mitochondria that may underlie the therapeutic benefit of using sMSCs to treat ischemic cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12017-022-08720-3. Springer US 2022-07-20 2023 /pmc/articles/PMC10025198/ /pubmed/35857254 http://dx.doi.org/10.1007/s12017-022-08720-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Gorsky, Anna
Monsour, Molly
Nguyen, Hung
Castelli, Vanessa
Lee, Jea-Young
Borlongan, Cesar V.
Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons
title Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons
title_full Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons
title_fullStr Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons
title_full_unstemmed Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons
title_short Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons
title_sort metabolic switching of cultured mesenchymal stem cells creates super mitochondria in rescuing ischemic neurons
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10025198/
https://www.ncbi.nlm.nih.gov/pubmed/35857254
http://dx.doi.org/10.1007/s12017-022-08720-3
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