Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

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Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes

Cellular Physiology and Biochemistry ◽

10.1159/000489739 ◽

2018 ◽

Vol 47 (1) ◽

pp. 11-25 ◽

Cited By ~ 48

Author(s):

Miguel Tofiño-Vian ◽

Maria Isabel Guillén ◽

María Dolores Pérez del Caz ◽

Antonio Silvestre ◽

María José Alcaraz

Keyword(s):

Nitric Oxide ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Conditioned Medium ◽

Extracellular Vesicles ◽

Prostaglandin E ◽

No Production ◽

Oa Chondrocytes ◽

Anti Inflammatory

Background/Aims: Chronic inflammation contributes to cartilage degeneration during the progression of osteoarthritis (OA). Adipose tissue-derived mesenchymal stem cells (AD-MSC) show great potential to treat inflammatory and degradative processes in OA and have demonstrated paracrine effects in chondrocytes. In the present work, we have isolated and characterized the extracellular vesicles from human AD-MSC to investigate their role in the chondroprotective actions of these cells. Methods: AD-MSC were isolated by collagenase treatment from adipose tissue from healthy individuals subjected to abdominal lipectomy surgery. Microvesicles and exosomes were obtained from conditioned medium by filtration and differential centrifugation. Chondrocytes from OA patients were used in primary culture and stimulated with 10 ng/ml interleukin(IL)-1β in the presence or absence of AD-MSC microvesicles, exosomes or conditioned medium. Protein expression was investigated by ELISA and immunofluorescence, transcription factor-DNA binding by ELISA, gene expression by real-time PCR, prostaglandin E2 (PGE2) by radioimmunoassay, and matrix metalloproteinase (MMP) activity and nitric oxide (NO) production by fluorometry. Results: In OA chondrocytes stimulated with IL-1β, microvesicles and exosomes reduced the production of inflammatory mediators tumor necrosis factor-α, IL-6, PGE2 and NO. The downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 would lead to the decreased PGE2 production while the effect on NO could depend on the reduction of inducible nitric oxide synthase expression. Treatment of OA chondrocytes with extracellular vesicles also decreased the release of MMP activity and MMP-13 expression whereas the production of the anti-inflammatory cytokine IL-10 and the expression of collagen II were significantly enhanced. The reduction of inflammatory and catabolic mediators could be the consequence of a lower activation of nuclear factor-κB and activator protein-1. The upregulation of annexin A1 specially in MV may contribute to the anti-inflammatory and chondroprotective effects of AD-MSC. Conclusions: Our data support the interest of AD-MSC extracellular vesicles to develop new therapeutic approaches in joint conditions.

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Adipogenic impairment of adipose tissue-derived mesenchymal stem cells in subjects with metabolic syndrome: possible protective role of FGF2

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-2256 ◽

2016 ◽

pp. jc.2016-2256 ◽

Cited By ~ 2

Author(s):

WILFREDO OLIVA-OLIVERA ◽

LETICIA COÍN-Aragüez ◽

SAID LHAMYANI ◽

MERCEDES CLEMENTE-POSTIGO ◽

JUAN ALCAIDE TORRES ◽

...

Keyword(s):

Metabolic Syndrome ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Protective Role

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Small extracellular vesicles from mesenchymal stem cells pre-conditioned with interferon-? can improve liver fibrosis by inducing anti-inflammatory macrophages with high migratory and phagocytotic abilities

Journal of Hepatology ◽

10.1016/s0168-8278(20)31531-2 ◽

2020 ◽

Vol 73 ◽

pp. S526

Author(s):

Suguru Takauchi ◽

Atsunori Tsuchiya ◽

Masaru Kumagai ◽

Takeki Sato ◽

Satoko Motegi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Fibrosis ◽

Extracellular Vesicles ◽

Anti Inflammatory ◽

Inflammatory Macrophages

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Parathyroid Hormone-Related Protein (PTHrP) Accelerates Soluble RANKL Signals for Downregulation of Osteogenesis of Bone Mesenchymal Stem Cells

Journal of Clinical Medicine ◽

10.3390/jcm8060836 ◽

2019 ◽

Vol 8 (6) ◽

pp. 836 ◽

Cited By ~ 3

Author(s):

Jeevithan Elango ◽

Saeed Ur Rahman ◽

Yves Henrotin ◽

José Eduardo Maté Sánchez de Val ◽

Bin Bao ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Parathyroid Hormone ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Related Protein ◽

Bone Mesenchymal Stem Cells ◽

Parathyroid Hormone Related Protein ◽

Receptor Activator

A recent study reported the expression of receptor activator of nuclear factor-κB (RANK) in mesenchymal stem cells (MSCs) surface that negatively regulates osteogenesis of MSCs. Empirical evidence from the previous study confirmed the role of parathyroid hormone-related protein (PTHrP) in osteoblastogenesis. However, it is necessary to understand the paracrine role of PTHrP and RANKL for osteogenesis in order to explore the hidden secrets in bone biology. Considering the above concept, paracrine cues of soluble-receptor activator of nuclear factor-κB ligand (sRANKL) and PTHrP in osteogenic differentiation of MSCs were investigated. Our results confirmed that sRANKL increased the expression of surface-RANK in MSCs at the earlier stage of osteogenesis, which was downregulated later in differentiated MSCs. In contrast, RANKL expression was low at the earlier stage of MSCs proliferation and high at the differentiation stage of MSCs, which may play a fundamental role in osteoclast formation. sRANKL downregulated osteogenesis of MSCs by decreasing progressive ankylosis (ANK) protein expression while PTHrP upregulated the osteogenic exploitive effect of sRANKL. Interestingly, when they were co-cultured with MSCs, T-lymphocytes expressed high membrane-RANKL levels that contribute to osteogenesis inhibition during MSC differentiation. Thus, our results disclose that sRANKL treatment downregulates osteogenesis of MSCs by increasing RANK expression at the earlier stage of differentiation and by inhibiting ANK. Further, we demonstrated that PTHrP accelerated the downregulating osteogenic effect of sRANKL.

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