Immunogenic potential of human bone marrow mesenchymal stromal cells is enhanced by hyperthermia
Copyright © 2018. Published by Elsevier Inc..
BACKGROUND AIMS: Bone marrow-derived mesenchymal stromal cells (MSCs) have been reported to suppress T-cell proliferation and used to alleviate the symptoms of graft-versus-host disease (GVHD). MSCs are a mixed cell population and at this time there are no tools to isolate the cells responsible for the T-cell suppression. We wanted to find a way to enhance the immune-modulatory actions of MSCs and tried varying the temperature at which they were cultured.
METHODS: We cultured human MSCs derived from healthy volunteers at different temperatures and tested their ability to switch macrophage character from pro-inflammatory to anti-inflammatory (M1 type to M2 type). Using an enzyme-linked immunosorbent assay (ELISA), we showed that when MSCs are cultured at higher temperatures their ability to induce co-cultured macrophages to produce more interleukin-10, (IL-10) (an anti-inflammatory cytokine) and less tumor necrosis factor alpha, (TNFα) (a pro-inflammatory cytokine) is increased. We performed Western blots and immunocytochemistry to screen for changes that might underlie this effect.
RESULTS: We found that in hyperthermia the heat shock protein, HSF1, translocated into the nucleus of MSCs. It appears to induce the COX2/PGE2 (Cyclooxygenase2/Prostaglandin E2) pathway described earlier as a major mechanism of MSC-directed immune-suppression.
CONCLUSION: Hyperthermia increases the efficacy of MSC-driven immune-suppression. We propose that changing the time of MSC administration to patients to mid-to-late afternoon when the body temperature is naturally highest might be beneficial. Warming the patient could also be considered.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Cytotherapy - 20(2018), 12 vom: 03. Dez., Seite 1437-1444 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
McClain-Caldwell, Ian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.10.2019 Date Revised 09.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jcyt.2018.10.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM290226244 |
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| 245 | 1 | 0 | |a Immunogenic potential of human bone marrow mesenchymal stromal cells is enhanced by hyperthermia |
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| 500 | |a Date Revised 09.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018. Published by Elsevier Inc. | ||
| 520 | |a BACKGROUND AIMS: Bone marrow-derived mesenchymal stromal cells (MSCs) have been reported to suppress T-cell proliferation and used to alleviate the symptoms of graft-versus-host disease (GVHD). MSCs are a mixed cell population and at this time there are no tools to isolate the cells responsible for the T-cell suppression. We wanted to find a way to enhance the immune-modulatory actions of MSCs and tried varying the temperature at which they were cultured | ||
| 520 | |a METHODS: We cultured human MSCs derived from healthy volunteers at different temperatures and tested their ability to switch macrophage character from pro-inflammatory to anti-inflammatory (M1 type to M2 type). Using an enzyme-linked immunosorbent assay (ELISA), we showed that when MSCs are cultured at higher temperatures their ability to induce co-cultured macrophages to produce more interleukin-10, (IL-10) (an anti-inflammatory cytokine) and less tumor necrosis factor alpha, (TNFα) (a pro-inflammatory cytokine) is increased. We performed Western blots and immunocytochemistry to screen for changes that might underlie this effect | ||
| 520 | |a RESULTS: We found that in hyperthermia the heat shock protein, HSF1, translocated into the nucleus of MSCs. It appears to induce the COX2/PGE2 (Cyclooxygenase2/Prostaglandin E2) pathway described earlier as a major mechanism of MSC-directed immune-suppression | ||
| 520 | |a CONCLUSION: Hyperthermia increases the efficacy of MSC-driven immune-suppression. We propose that changing the time of MSC administration to patients to mid-to-late afternoon when the body temperature is naturally highest might be beneficial. Warming the patient could also be considered | ||
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| 700 | 1 | |a Mayer, Balazs |e verfasserin |4 aut | |
| 700 | 1 | |a Krepuska, Miklos |e verfasserin |4 aut | |
| 700 | 1 | |a Boyajian, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Myneni, Vamsee |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Daniel |e verfasserin |4 aut | |
| 700 | 0 | |a GENOMICS AND COMPUTATIONAL BIOLOGY CORE |e verfasserin |4 aut | |
| 700 | 1 | |a Marko, Karoly |e verfasserin |4 aut | |
| 700 | 1 | |a Nemeth, Krisztian |e verfasserin |4 aut | |
| 700 | 1 | |a Mezey, Eva |e verfasserin |4 aut | |
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