Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies.

dc.contributor.author

Min, Hyunjung

dc.contributor.author

Xu, Li

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Parrott, Roberta

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Overall, Christopher C

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Lillich, Melina

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Rabjohns, Emily M

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Rampersad, Rishi R

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Tarrant, Teresa K

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Meadows, Norin

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Fernandez-Castaneda, Anthony

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Gaultier, Alban

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Kurtzberg, Joanne

dc.contributor.author

Filiano, Anthony J

dc.date.accessioned

2022-03-23T14:47:07Z

dc.date.available

2022-03-23T14:47:07Z

dc.date.issued

2021-01

dc.date.updated

2022-03-23T14:47:06Z

dc.description.abstract

Mesenchymal stromal cells (MSCs) are widely used in clinical trials because of their ability to modulate inflammation. The success of MSCs has been variable over 25 years, most likely due to an incomplete understanding of their mechanism. After MSCs are injected, they traffic to the lungs and other tissues where they are rapidly cleared. Despite being cleared, MSCs suppress the inflammatory response in the long term. Using human cord tissue-derived MSCs (hCT-MSCs), we demonstrated that hCT-MSCs directly interact and reprogram monocytes and macrophages. After engaging hCT-MSCs, monocytes and macrophages engulfed cytoplasmic components of live hCT-MSCs, then downregulated gene programs for antigen presentation and costimulation, and functionally suppressed the activation of helper T cells. We determined that low-density lipoprotein receptor-related proteins on monocytes and macrophages mediated the engulfment of hCT-MSCs. Since a large amount of cellular information can be packaged in cytoplasmic RNA processing bodies (p-bodies), we generated p-body deficient hCT-MSCs and confirmed that they failed to reprogram monocytes and macrophages in vitro and in vivo. hCT-MSCs suppressed an inflammatory response caused by a nasal lipopolysaccharide challenge. Although both control and p-body deficient hCT-MSCs were engulfed by infiltrating lung monocytes and macrophages, p-body deficient hCT-MSCs failed to suppress inflammation and downregulate MHC-II. Overall, we identified a novel mechanism by which hCT-MSCs indirectly suppressed a T-cell response by directly interacting and reprogramming monocytes and macrophages via p-bodies. The results of this study suggest a novel mechanism for how MSCs can reprogram the inflammatory response and have long-term effects to suppress inflammation.

dc.identifier.issn

1066-5099

dc.identifier.issn

1549-4918

dc.identifier.uri

https://hdl.handle.net/10161/24563

dc.language

eng

dc.publisher

Oxford University Press (OUP)

dc.relation.ispartof

Stem cells (Dayton, Ohio)

dc.relation.isversionof

10.1002/stem.3292

dc.subject

Monocytes

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Macrophages

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Mesenchymal Stem Cells

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Animals

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Humans

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Mice

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Mesenchymal Stem Cell Transplantation

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Heterografts

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Cellular Reprogramming

dc.title

Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies.

dc.type

Journal article

duke.contributor.orcid

Tarrant, Teresa K|0000-0003-4067-5363

duke.contributor.orcid

Kurtzberg, Joanne|0000-0002-3370-0703

pubs.begin-page

115

pubs.end-page

128

pubs.issue

1

pubs.organisational-group

Duke

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School of Medicine

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Basic Science Departments

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Clinical Science Departments

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Immunology

pubs.organisational-group

Medicine

pubs.organisational-group

Pathology

pubs.organisational-group

Pediatrics

pubs.organisational-group

Medicine, Rheumatology and Immunology

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Duke Cancer Institute

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Institutes and Provost's Academic Units

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Initiatives

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Neurosurgery

pubs.organisational-group

Duke Innovation & Entrepreneurship

pubs.organisational-group

Pediatrics, Transplant and Cellular Therapy

pubs.publication-status

Published

pubs.volume

39

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