Mesenchymal stem/stromal cells (MSCs): Role as guardians of inflammation

Darwin J. Prockop, Joo Youn Oh

Research output: Contribution to journalReview article

447 Citations (Scopus)

Abstract

Recent observations have demonstrated that one of the functions of mesenchymal stem/stromal cells (MSCs) is to serve as guardians against excessive inflammatory responses. One mode of action of the cells is that they are activated to express the interleukin (IL)-1 receptor antagonist. A second mode of action is to create a negative feedback loop in which tumor necrosis factor-α (TNF-α) and other proinflammatory cytokines from resident macrophages activate MSCs to secrete the multifunctional anti-inflammatory protein TNF-α stimulated gene/protein 6 (TSG-6). The TSG-6 then reduces nuclear factor-B (NF-B) signaling in the resident macrophages and thereby modulates the cascade of proinflammatory cytokines. A third mode of action is to create a second negative feedback loop whereby lipopolysaccharide, TNF-α, nitric oxide, and perhaps other damage-associated molecular patterns (DAMPs) from injured tissues and macrophages activate MSCs to secrete prostaglandin E 2 (PGE 2). The PGE 2 converts macrophages to the phenotype that secretes IL-10. There are also suggestions that MSCs may produce anti-inflammatory effects through additional modes of action including activation to express the antireactive oxygen species protein stanniocalcin-1.

Original languageEnglish
Pages (from-to)14-20
Number of pages7
JournalMolecular Therapy
Volume20
Issue number1
DOIs
StatePublished - Jan 2012

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Mesenchymal Stromal Cells
Inflammation
Macrophages
Tumor Necrosis Factor-alpha
Prostaglandins E
Proteins
Anti-Inflammatory Agents
Cytokines
Interleukin-1 Receptors
Interleukin-10
Lipopolysaccharides
Nitric Oxide
Oxygen
Phenotype

Cite this

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abstract = "Recent observations have demonstrated that one of the functions of mesenchymal stem/stromal cells (MSCs) is to serve as guardians against excessive inflammatory responses. One mode of action of the cells is that they are activated to express the interleukin (IL)-1 receptor antagonist. A second mode of action is to create a negative feedback loop in which tumor necrosis factor-α (TNF-α) and other proinflammatory cytokines from resident macrophages activate MSCs to secrete the multifunctional anti-inflammatory protein TNF-α stimulated gene/protein 6 (TSG-6). The TSG-6 then reduces nuclear factor-B (NF-B) signaling in the resident macrophages and thereby modulates the cascade of proinflammatory cytokines. A third mode of action is to create a second negative feedback loop whereby lipopolysaccharide, TNF-α, nitric oxide, and perhaps other damage-associated molecular patterns (DAMPs) from injured tissues and macrophages activate MSCs to secrete prostaglandin E 2 (PGE 2). The PGE 2 converts macrophages to the phenotype that secretes IL-10. There are also suggestions that MSCs may produce anti-inflammatory effects through additional modes of action including activation to express the antireactive oxygen species protein stanniocalcin-1.",
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Mesenchymal stem/stromal cells (MSCs) : Role as guardians of inflammation. / Prockop, Darwin J.; Oh, Joo Youn.

In: Molecular Therapy, Vol. 20, No. 1, 01.2012, p. 14-20.

Research output: Contribution to journalReview article

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