Immunogenic potential of human bone marrow mesenchymal stromal cells is enhanced by hyperthermia.
Cytotherapy
; 20(12): 1437-1444, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30389270
ABSTRACT
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Mesenquimais
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Hipertermia Induzida
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Macrófagos
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article