Stem Cells Transl Med. 2016 Jul 8. pii: sctm.2015-0217. [Epub ahead of print]

Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF-β Secretion.

Noh MY¹, Lim SM¹, Oh KW¹, Cho KA², Park J¹, Kim KS³, Lee SJ¹, Kwon MS⁴, Kim SH⁵.

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Abstract

: The regulation of microglial cell phenotype is a potential therapeutic intervention in neurodegenerative disease. Previously, we reported that transforming growth factor-β (TGF-β) levels in mesenchymal stromal cells (MSCs) could be used as potential biological markers to predict the effectiveness of autologous MSC therapy in patients with amyotrophic lateral sclerosis. However, the underlying mechanism of TGF-β in MSCs was not fully elucidated in determining the functional properties of microglia. In this study, we aimed to clarify the role of TGF-β that is involved in MSC effectiveness, especially focusing on microglia functional properties that play a pivotal role in neuroinflammation. We found that MSC-conditioned media (MSC-CM) inhibited proinflammatory cytokine expression, restored alternative activated microglia phenotype markers (fractalkine receptor, mannose receptor, CD200 receptor), and enhanced phagocytosis in lipopolysaccharide (LPS)-stimulated microglia. In addition, TGF-β in MSC-CM played a major role in these effects by inhibiting the nuclear factor-κB pathway and restoring the TGF-β pathway in LPS-stimulated microglia. Recombinant TGF-β also induced similar effects to MSC-CM in LPS-stimulated microglia. Therefore, we propose that MSCs can modulate the functional properties of microglia via TGF-β secretion, switching them from a classically activated phenotype to an inflammation-resolving phenotype. The latter role may be associated with the inhibition of neuroinflammatory processes in neurodegenerative disorders.