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

Title
Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF-beta Secretion
Author
노민영
Keywords
Mesenchymal stem cells; Microglia; TGF-beta; Neurodegenerative diseases
Issue Date
2016-07
Publisher
ALPHAMED PRESS
Citation
STEM CELLS TRANSLATIONAL MEDICINE (2016), v. 5, NO. 11, Page. 1538-1549
Abstract
The regulation of microglial cell phenotype is a potential therapeutic intervention in neurodegenerative disease. Previously, we reported that transforming growth factor-beta (TGF-beta) 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-beta in MSCs was not fully elucidated in determining the functional properties of microglia. In this study, we aimed to clarify the role of TGF-beta 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-beta in MSC-CM played a major role in these effects by inhibiting the nuclear factor-kappa B pathway and restoring the TGF-beta pathway in LPS-stimulated microglia. Recombinant TGF-beta 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-beta 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.
URI
https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.5966/sctm.2015-0217http://repository.hanyang.ac.kr/handle/20.500.11754/74466
ISSN
2157-6564; 2157-6580
DOI
10.5966/sctm.2015-0217
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RESEARCH INSTITUTE[S](부설연구소) > ETC
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