Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF‐β Secretion. (8th July 2016)

• Record Type: Journal Article
• Authors: Noh, Min Young; Lim, Su Min; Oh, Ki-Wook; Cho, Kyung-Ah; Park, Jinseok; Kim, Kyung-Suk; Lee, Su-Jung; Kwon, Min-Soo; Kim, Seung Hyun
• Is Part Of: Stem cells translational medicine. Volume 5:Number 11(2016)
• Page Start: 1538
• Page End: 1549
• Publication Date: 2016-07-08
• Subjects: Mesenchymal stem cells -- Microglia -- TGF-β -- Neurodegenerative diseases; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2015-0217
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract : Mesenchymal stromal cell‐conditioned media (MSC‐CM) inhibited proinflammatory cytokine expression, restored alternative activated microglia phenotype markers, and enhanced phagocytosis in lipopolysaccharide (LPS)‐stimulated microglia. Transforming growth factor‐β (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 effects similar to those of MSC‐CM in LPS‐stimulated microglia. Abstract : Acknowledgements: 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. The results of this study showed that microglia functional properties may be modulated depending on the composition and quantity of mesenchymal stromal cell (MSC)‐secreting factors. Transforming growth factor (TGF)‐β is proposed as a modulator of microglia functional properties among MSC‐secreting factors, and this study aligns with a previous clinical study by these same authors. TGF‐β releasing capacity could be an important factor enhancing the therapeutic efficacy of MSCs in clinical trials.