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Cytotherapy. 2018 Dec;20(12):1437-1444. doi: 10.1016/j.jcyt.2018.10.002. Epub 2018 Oct 31.

Immunogenic potential of human bone marrow mesenchymal stromal cells is enhanced by hyperthermia.

Author information

1
Adult Stem Cell Section, National Institute of Craniofacial and Dental Research, Bethesda, Maryland, USA.
2
Adult Stem Cell Section, National Institute of Deafness and Other Communication Disorders, Genomics and Computational Biology Core, National Institutes of Health, Bethesda, Maryland, USA.
3
Adult Stem Cell Section, National Institute of Craniofacial and Dental Research, Bethesda, Maryland, USA. Electronic address: mezeye@mail.nih.gov.

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.

KEYWORDS:

M2); high temperature; human bone marrow stromal cells; mesenchymal stromal cells; priming mesenchymal stromal cells; pro- and anti-inflammatory macrophages (M1

PMID:
30389270
DOI:
10.1016/j.jcyt.2018.10.002

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