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Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ2/PPAR?/TGF-?1 pathway.

ABSTRACT: Bone marrow mesenchymal stem cells (BMMSCs) have been used to treat a variety of autoimmune diseases in clinics. However, the therapeutic effects are largely dependent on the immunomodulatory capacity of culture-expanded BMMSCs. In the present study, we show that aspirin (acetylsalicylic acid, ASA)-treated BMMSCs have significantly improved immunomodulatory function, as indicated by upregulation of regulatory T cells (Tregs) and downregulation of Th17 cells via the 15d-PGJ2/PPAR?/TGF-?1 pathway. Furthermore, the therapeutic effect of ASA-pretreated BMMSCs was confirmed in a dextran sodium sulfate-induced experimental colitis mouse model, in which systemic infusion of ASA-pretreated BMMSCs significantly ameliorated disease activity index and colonic inflammation, along with an increased number of Tregs and decreased number of Th17 cells. Taken together, our results suggest that aspirin treatment is a feasible strategy to promote BMMSC-based immunomodulation.

SUBMITTER: Tang J

PROVIDER: S-EPMC4142833 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ2/PPARγ/TGF-β1 pathway.

Tang Jianxia J Xiong Jimin J Wu Tingting T Tang Zhangui Z Ding Gang G Zhang Chunmei C Wang Songlin S Liu Yi Y

Stem cells and development 20140701 17

Bone marrow mesenchymal stem cells (BMMSCs) have been used to treat a variety of autoimmune diseases in clinics. However, the therapeutic effects are largely dependent on the immunomodulatory capacity of culture-expanded BMMSCs. In the present study, we show that aspirin (acetylsalicylic acid, ASA)-treated BMMSCs have significantly improved immunomodulatory function, as indicated by upregulation of regulatory T cells (Tregs) and downregulation of Th17 cells via the 15d-PGJ2/PPARγ/TGF-β1 pathway. ...[more]

PMID: 24730450

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Project description:: The regulation of microglial cell phenotype is a potential therapeutic intervention in neurodegenerative disease. Previously, we reported that transforming growth factor-? (TGF-?) 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-? in MSCs was not fully elucidated in determining the functional properties of microglia. In this study, we aimed to clarify the role of TGF-? 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-? in MSC-CM played a major role in these effects by inhibiting the nuclear factor-?B pathway and restoring the TGF-? pathway in LPS-stimulated microglia. Recombinant TGF-? 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-? 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.SignificanceThe 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)-? 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-? releasing capacity could be an important factor enhancing the therapeutic efficacy of MSCs in clinical trials.

Dataset Information

Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ2/PPAR?/TGF-?1 pathway.

Publications

Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ2/PPARγ/TGF-β1 pathway.

Similar Datasets

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