Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes

Accumulating evidence has shown that the paracrine factors derived from mesenchymal stem cells (MSCs) are capable of regulating the immune system via interaction with various immune cells. In this study, adipose-derived MSCs (AdMSCs) and human peripheral blood monocytes (PBMCs) were isolated and cul...

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Main Authors: June Seok Heo, Youjeong Choi, Hyun Ok Kim
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/7921760
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author June Seok Heo
Youjeong Choi
Hyun Ok Kim
author_facet June Seok Heo
Youjeong Choi
Hyun Ok Kim
author_sort June Seok Heo
collection DOAJ
description Accumulating evidence has shown that the paracrine factors derived from mesenchymal stem cells (MSCs) are capable of regulating the immune system via interaction with various immune cells. In this study, adipose-derived MSCs (AdMSCs) and human peripheral blood monocytes (PBMCs) were isolated and cultured to examine the effects of MSC-induced macrophages (iMΦ) on inflammation and immune modulation. Indirect coculture with MSCs increased the expression of arginase-1 and mannose receptor (CD206), markers of activated M2 macrophages, in the PBMCs demonstrating that MSC-secreted factors promoted M2-MΦ polarization. Additionally, iMΦ exhibited a similar higher inhibitory effect on the growth of activated T cells compared to that in the other groups (AdMSCs only, AdMSCs plus iMΦ), implying that iMΦ can play a sufficient functional role. Interestingly, the population of FoxP3 Treg cells significantly increased when cocultured with iMΦ, suggesting that iMΦ have an immunomodulatory effect on the Treg cells through the modulation of the FoxP3 expression. Notably, iMΦ expressed high levels of immunosuppressive and anti-inflammatory cytokines, namely IL-10 and TSG-6. Furthermore, we confirmed that the AdMSC-derived exosomes modulated macrophage polarization by upregulating the expression of M2 macrophage markers. Conclusively, our results suggest that iMΦ play a significant role in regulating the immunomodulatory- and inflammatory-mediated responses. Thus, iMΦ may be used as a novel stem cell-based cell-free therapy for the treatment of immune-mediated inflammatory disorders.
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spelling doaj-art-e50d7f706c4044e087abed8ea7152f572025-02-03T05:51:51ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/79217607921760Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through ExosomesJune Seok Heo0Youjeong Choi1Hyun Ok Kim2Cell Therapy Center, Severance Hospital, Seoul 03722, Republic of KoreaCell Therapy Center, Severance Hospital, Seoul 03722, Republic of KoreaCell Therapy Center, Severance Hospital, Seoul 03722, Republic of KoreaAccumulating evidence has shown that the paracrine factors derived from mesenchymal stem cells (MSCs) are capable of regulating the immune system via interaction with various immune cells. In this study, adipose-derived MSCs (AdMSCs) and human peripheral blood monocytes (PBMCs) were isolated and cultured to examine the effects of MSC-induced macrophages (iMΦ) on inflammation and immune modulation. Indirect coculture with MSCs increased the expression of arginase-1 and mannose receptor (CD206), markers of activated M2 macrophages, in the PBMCs demonstrating that MSC-secreted factors promoted M2-MΦ polarization. Additionally, iMΦ exhibited a similar higher inhibitory effect on the growth of activated T cells compared to that in the other groups (AdMSCs only, AdMSCs plus iMΦ), implying that iMΦ can play a sufficient functional role. Interestingly, the population of FoxP3 Treg cells significantly increased when cocultured with iMΦ, suggesting that iMΦ have an immunomodulatory effect on the Treg cells through the modulation of the FoxP3 expression. Notably, iMΦ expressed high levels of immunosuppressive and anti-inflammatory cytokines, namely IL-10 and TSG-6. Furthermore, we confirmed that the AdMSC-derived exosomes modulated macrophage polarization by upregulating the expression of M2 macrophage markers. Conclusively, our results suggest that iMΦ play a significant role in regulating the immunomodulatory- and inflammatory-mediated responses. Thus, iMΦ may be used as a novel stem cell-based cell-free therapy for the treatment of immune-mediated inflammatory disorders.http://dx.doi.org/10.1155/2019/7921760
spellingShingle June Seok Heo
Youjeong Choi
Hyun Ok Kim
Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
Stem Cells International
title Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
title_full Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
title_fullStr Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
title_full_unstemmed Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
title_short Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes
title_sort adipose derived mesenchymal stem cells promote m2 macrophage phenotype through exosomes
url http://dx.doi.org/10.1155/2019/7921760
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AT youjeongchoi adiposederivedmesenchymalstemcellspromotem2macrophagephenotypethroughexosomes
AT hyunokkim adiposederivedmesenchymalstemcellspromotem2macrophagephenotypethroughexosomes