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Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells

BACKGROUND: Greater knowledge of mesenchymal stromal cell (MSC)-based therapies is driving the research into their secretome, identified as the main element responsible for their therapeutic effects. The aim of this study is to characterize the individual variability of the secretome of adipose tiss...

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Autores principales: Baldassarro, Vito Antonio, Perut, Francesca, Cescatti, Maura, Pinto, Valentina, Fazio, Nicola, Alastra, Giuseppe, Parziale, Valentina, Bassotti, Alessandra, Fernandez, Mercedes, Giardino, Luciana, Baldini, Nicola, Calzà, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173531/
https://www.ncbi.nlm.nih.gov/pubmed/37170115
http://dx.doi.org/10.1186/s13287-023-03344-1
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author Baldassarro, Vito Antonio
Perut, Francesca
Cescatti, Maura
Pinto, Valentina
Fazio, Nicola
Alastra, Giuseppe
Parziale, Valentina
Bassotti, Alessandra
Fernandez, Mercedes
Giardino, Luciana
Baldini, Nicola
Calzà, Laura
author_facet Baldassarro, Vito Antonio
Perut, Francesca
Cescatti, Maura
Pinto, Valentina
Fazio, Nicola
Alastra, Giuseppe
Parziale, Valentina
Bassotti, Alessandra
Fernandez, Mercedes
Giardino, Luciana
Baldini, Nicola
Calzà, Laura
author_sort Baldassarro, Vito Antonio
collection PubMed
description BACKGROUND: Greater knowledge of mesenchymal stromal cell (MSC)-based therapies is driving the research into their secretome, identified as the main element responsible for their therapeutic effects. The aim of this study is to characterize the individual variability of the secretome of adipose tissue-derived MSCs (adMSCs) with regard to potential therapeutical applications in neurology. METHODS: adMSCs were isolated from the intact adipose tissue of ten subjects undergoing abdominal plastic surgery or reduction mammoplasty. Two commercial lines were also included. We analyzed the expansion rate, production, and secretion of growth factors of interest for neurological applications (VEGF-A, BDNF, PDGF-AA and AA/BB, HGF, NGF, FGF-21, GDNF, IGF-I, IGF-II, EGF and FGF-2). To correlate these characteristics with the biological effects on the cellular targets, we used individual media conditioned with adMSCs from the various donors on primary cultures of neurons/astrocytes and oligodendrocyte precursor cells (OPCs) exposed to noxious stimuli (oxygen–glucose deprivation, OGD) to evaluate their protective and promyelinating properties, using MSC medium as a control group. RESULTS: The MSC secretome showed significant individual variability within the considered population with regard to PDGF-AA, PDGF-AB/BB, VEGF-A and BDNF. None of the MSC-derived supernatants affected neuron viability in normoxia, while substantial protection by high BDNF-containing conditioned MSC medium was observed in neuronal cultures exposed to OGD conditions. In OPC cultures, the MSC-derived supernatants protected cells from OGD-induced cell death, also increasing the differentiation in mature oligodendrocytes. Neuroprotection showed a positive correlation with VEGF-A, BDNF and PDGF-AA concentrations in the culture supernatants, and an inverse correlation with HGF, while OPC differentiation following OGD was positively correlated to PDGF-AA concentration. CONCLUSIONS: Despite the limited number of adMSC donors, this study showed significant individual variability in the biological properties of interest for neurological applications for adMSC secretome, an under-researched aspect which may represent an important step in the translation of MSC-derived acellular products to clinical practice. We also showed the potential protection capability of MSC conditioned medium on neuronal and oligodendroglial lineages exposed to oxygen–glucose deprivation. These effects are directly correlated to the concentration of specific growth factors, and indicate that the remyelination should be included as a primary target in MSC-based therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03344-1.
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spelling pubmed-101735312023-05-12 Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells Baldassarro, Vito Antonio Perut, Francesca Cescatti, Maura Pinto, Valentina Fazio, Nicola Alastra, Giuseppe Parziale, Valentina Bassotti, Alessandra Fernandez, Mercedes Giardino, Luciana Baldini, Nicola Calzà, Laura Stem Cell Res Ther Research BACKGROUND: Greater knowledge of mesenchymal stromal cell (MSC)-based therapies is driving the research into their secretome, identified as the main element responsible for their therapeutic effects. The aim of this study is to characterize the individual variability of the secretome of adipose tissue-derived MSCs (adMSCs) with regard to potential therapeutical applications in neurology. METHODS: adMSCs were isolated from the intact adipose tissue of ten subjects undergoing abdominal plastic surgery or reduction mammoplasty. Two commercial lines were also included. We analyzed the expansion rate, production, and secretion of growth factors of interest for neurological applications (VEGF-A, BDNF, PDGF-AA and AA/BB, HGF, NGF, FGF-21, GDNF, IGF-I, IGF-II, EGF and FGF-2). To correlate these characteristics with the biological effects on the cellular targets, we used individual media conditioned with adMSCs from the various donors on primary cultures of neurons/astrocytes and oligodendrocyte precursor cells (OPCs) exposed to noxious stimuli (oxygen–glucose deprivation, OGD) to evaluate their protective and promyelinating properties, using MSC medium as a control group. RESULTS: The MSC secretome showed significant individual variability within the considered population with regard to PDGF-AA, PDGF-AB/BB, VEGF-A and BDNF. None of the MSC-derived supernatants affected neuron viability in normoxia, while substantial protection by high BDNF-containing conditioned MSC medium was observed in neuronal cultures exposed to OGD conditions. In OPC cultures, the MSC-derived supernatants protected cells from OGD-induced cell death, also increasing the differentiation in mature oligodendrocytes. Neuroprotection showed a positive correlation with VEGF-A, BDNF and PDGF-AA concentrations in the culture supernatants, and an inverse correlation with HGF, while OPC differentiation following OGD was positively correlated to PDGF-AA concentration. CONCLUSIONS: Despite the limited number of adMSC donors, this study showed significant individual variability in the biological properties of interest for neurological applications for adMSC secretome, an under-researched aspect which may represent an important step in the translation of MSC-derived acellular products to clinical practice. We also showed the potential protection capability of MSC conditioned medium on neuronal and oligodendroglial lineages exposed to oxygen–glucose deprivation. These effects are directly correlated to the concentration of specific growth factors, and indicate that the remyelination should be included as a primary target in MSC-based therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03344-1. BioMed Central 2023-05-11 /pmc/articles/PMC10173531/ /pubmed/37170115 http://dx.doi.org/10.1186/s13287-023-03344-1 Text en © The Author(s) 2023 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Baldassarro, Vito Antonio
Perut, Francesca
Cescatti, Maura
Pinto, Valentina
Fazio, Nicola
Alastra, Giuseppe
Parziale, Valentina
Bassotti, Alessandra
Fernandez, Mercedes
Giardino, Luciana
Baldini, Nicola
Calzà, Laura
Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
title Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
title_full Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
title_fullStr Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
title_full_unstemmed Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
title_short Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
title_sort intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173531/
https://www.ncbi.nlm.nih.gov/pubmed/37170115
http://dx.doi.org/10.1186/s13287-023-03344-1
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