Mesenchymal stem cell–secreted extracellular vesicles carrying TGF‐β1 up‐regulate miR‐132 and promote mouse M2 macrophage polarization

Wang, Yongqi; Han, Baohui; Wang, Yingbin; Wang, Chunai; Zhang, Hong; Xue, Jianjun; Wang, Xiaoqing; Niu, Tingting; Niu, Zhenxing; Chen, Yuhe

doi:10.1111/jcmm.15860

Cited by 38 publications

(21 citation statements)

References 38 publications

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“…Resting MSCs release exosomes and MVs with positivity for the characteristic markers of these cells (CD105, CD90, and CD73) and the absence of MHC-I, MHC-II, CD34, and CD45 [48,[90][91][92][93][94]122,123]; they also transport immunoregulatory molecules such as PD-L1, Gal-1, and TGF-β [90,124] (Figure 3).…”

Section: Immunoregulation Mediated By Extracellular Vesiclesmentioning

confidence: 99%

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

López-García

Castro-Manrreza

2021

IJMS

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Mesenchymal stem/stromal cells (MSCs) have an immunoregulatory capacity and have been used in different clinical protocols requiring control of the immune response. However, variable results have been obtained, mainly due to the effect of the microenvironment on the induction, increase, and maintenance of MSC immunoregulatory mechanisms. In addition, the importance of cell–cell contact for MSCs to efficiently modulate the immune response has recently been highlighted. Because these interactions would be difficult to achieve in the physiological context, the release of extracellular vesicles (EVs) and their participation as intermediaries of communication between MSCs and immune cells becomes relevant. Therefore, this article focuses on analyzing immunoregulatory mechanisms mediated by cell contact, highlighting the importance of intercellular adhesion molecule-1 (ICAM-1) and the participation of EVs. Moreover, the effects of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), the main cytokines involved in MSC activation, are examined. These cytokines, when used at the appropriate concentrations and times, would promote increases in the expression of immunoregulatory molecules in the cell and allow the acquisition of EVs enriched with these molecules. The establishment of certain in vitro activation guidelines will facilitate the design of conditioning protocols to obtain functional MSCs or EVs in different pathophysiological conditions.

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Section: Immunoregulation Mediated By Extracellular Vesiclesmentioning

confidence: 99%

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

López-García

Castro-Manrreza

2021

IJMS

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“…These effects can be explained in part through microRNA, as microRNAs such as miR-132 are highly upregulated during inflammation and can induce M2 polarization through regulation of TLRs [285][286][287]. Studies have found that miR-132 located within MSC-Exos can elevate IL-10 expression and decrease levels of NF-кB, IL-6 and IL-1β in favor of inflammation resolution [288][289][290]. Broadly, exosomes have shown significant beneficial effects on proliferation, collagen deposition, and angiogenesis, even in states of chronic wounds and comorbidities such as diabetes [272,273,291].…”

Section: Wound Healingmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

Hade

Suire

Suo

2021

Cells

231

154

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Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that are then released into the extracellular space through a merging of the multivesicular body with the plasma membrane. These vesicles are secreted by almost all cell types to aid in a vast array of cellular functions, including intercellular communication, cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. This ability to contribute to several distinct processes is due to the complexity of exosomes, as they carry a multitude of signaling moieties, including proteins, lipids, cell surface receptors, enzymes, cytokines, transcription factors, and nucleic acids. The favorable biological properties of exosomes including biocompatibility, stability, low toxicity, and proficient exchange of molecular cargos make exosomes prime candidates for tissue engineering and regenerative medicine. Exploring the functions and molecular payloads of exosomes can facilitate tissue regeneration therapies and provide mechanistic insight into paracrine modulation of cellular activities. In this review, we summarize the current knowledge of exosome biogenesis, composition, and isolation methods. We also discuss emerging healing properties of exosomes and exosomal cargos, such as microRNAs, in brain injuries, cardiovascular disease, and COVID-19 amongst others. Overall, this review highlights the burgeoning roles and potential applications of exosomes in regenerative medicine.

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“…Several studies suggest a key role of PGE2, as the inhibition of PGE2 or the cyclooxygenase-2 (COX2) pathway abrogated the observed inhibitory effects ( Németh et al, 2009 ; Jin et al, 2019 ; Ortiz-Virumbrales et al, 2020 ). Previous studies using AD- or BM-MSCs indicated that the paracrine action is partially mediated by exosomes ( Biswas et al, 2019 ; Cho et al, 2019 ; He et al, 2019 ; Liu et al, 2019b ; Wang et al, 2020b ). The exosomes contained TGF-β, C1q, semaphorins, and micro (mi) RNAs, regulating the macrophage polarization and inducing overexpression of programmed cell death 1 ligand 1 (PD-L1).…”

Section: Modulation Of Innate Immunity By Mscsmentioning

confidence: 99%

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update

Müller

Tunger

Wobus

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stromal cells (MSCs) are characterized by an extraordinary capacity to modulate the phenotype and functional properties of various immune cells that play an essential role in the pathogenesis of inflammatory disorders. Thus, MSCs efficiently impair the phagocytic and antigen-presenting capacity of monocytes/macrophages and promote the expression of immunosuppressive molecules such as interleukin (IL)-10 and programmed cell death 1 ligand 1 by these cells. They also effectively inhibit the maturation of dendritic cells and their ability to produce proinflammatory cytokines and to stimulate potent T-cell responses. Furthermore, MSCs inhibit the generation and proinflammatory properties of CD4+ T helper (Th)1 and Th17 cells, while they promote the proliferation of regulatory T cells and their inhibitory capabilities. MSCs also impair the expansion, cytokine secretion, and cytotoxic activity of proinflammatory CD8+ T cells. Moreover, MSCs inhibit the differentiation, proliferation, and antibody secretion of B cells, and foster the generation of IL-10-producing regulatory B cells. Various cell membrane-associated and soluble molecules essentially contribute to these MSC-mediated effects on important cellular components of innate and adaptive immunity. Due to their immunosuppressive properties, MSCs have emerged as promising tools for the treatment of inflammatory disorders such as acute graft-versus-host disease, graft rejection in patients undergoing organ/cell transplantation, and autoimmune diseases.

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Mesenchymal stem cell–secreted extracellular vesicles carrying TGF‐β1 up‐regulate miR‐132 and promote mouse M2 macrophage polarization

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 38 publications

References 38 publications

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update

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