The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming

Luque‐Campos, Noymar; Bustamante-Barrientos, Felipe A.; Pradenas, Carolina; Garcia, Claudia M.; Araya, María Jesús; Bohaud, Candice; Contreras-López, Rafael; Elizondo‐Vega, Roberto; Djouad, Farida; Luz‐Crawford, Patricia; Vega-Letter, Ana María

doi:10.3389/fimmu.2021.624746

Cited by 34 publications

(21 citation statements)

References 195 publications

(330 reference statements)

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“…It can thus be hypothesized that macrophages respond to the necrotic disrupted bone marrow mesenchymal cells. The crosstalk between mesenchymal cells and macrophages in the development of disease and maintenance of homeostasis of inflammatory microenvironments became a research focus [ 18 , 19 ]. However, evidence supporting a role of damaged mesenchymal cell to modulate osteoclastogenesis and macrophage polarization [ 20 ] is limited.…”

Section: Introductionmentioning

confidence: 99%

Damaged Mesenchymal Cells Dampen the Inflammatory Response of Macrophages and the Formation of Osteoclasts

Panahipour

Abbasabadi

Kaiser

et al. 2022

JCM

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Damage to mesenchymal cells occurs by dental implant drills as a consequence of shear forces and heat generation. However, how the damaged mesenchymal cells can affect the polarization of macrophages and their differentiation into osteoclastogenesis is not fully understood. To simulate cell damage, we exposed suspended ST2 murine bone marrow stromal cells to freeze/thawing or sonication cycles, followed by centrifugation. We then evaluated the lysates for their capacity to modulate lipopolysaccharide-induced macrophage polarization and RANKL-MCSF-TGF-β-induced osteoclastogenesis. We report that lysates of ST2, particularly when sonicated, greatly diminished the expression of inflammatory IL6 and COX2 as well as moderately increased arginase 1 in primary macrophages. That was confirmed by lysates obtained from the osteocytic cell line IDG-SW3. Moreover, the ST2 lysate lowered the phosphorylation of p65 and p38 as well as the nuclear translocation of p65. We further show herein that lysates of damaged ST2 reduced the formation of osteoclast-like cells characterized by their multinuclearity and the expression of tartrate-resistant phosphatase and cathepsin K. Taken together, our data suggest that thermal and mechanical damage of mesenchymal cells causes the release of as-yet-to-be-defined molecules that dampen an inflammatory response and the formation of osteoclasts in vitro.

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Section: Introductionmentioning

confidence: 99%

Damaged Mesenchymal Cells Dampen the Inflammatory Response of Macrophages and the Formation of Osteoclasts

Panahipour

Abbasabadi

Kaiser

et al. 2022

JCM

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“…Interleukin-10, also associated with the expression of ASPS, IGF1 and its receptor IRS-1, clearly has chondroprotection activity, stimulating the expression of collagen type II and proteoglycan and regulating the maintenance of tissue integrity [ 48 ]. Moreover, our results demonstrated that adipose tissue also hosts chemokines such as 11β-HSD1, PPARγ, and adiponectin which have been shown to contribute to immunoregulation through modulation of hMSC metabolism [ 49 , 50 ], but also chemokines such as MCP1, Visfatin, and Resistin which have been shown to contribute to immunoregulation through modulation of macrophages plasticity [ 51 ]. Beyond that, adiponectin, ASPS, MCP1, Visfatin, and Resistin, when taken together, prove that they can contribute to the diagnosis of OA, which is consistent with our results.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions

Francesco

Riccio

Busato

et al. 2021

Animals

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Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses.

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“…Pro-inflammatory macrophage polarization is characterized by enhanced glycolysis and pentose phosphate pathways and decreased oxidative phosphorylation. In contrast, anti-inflammatory macrophage polarization is characterized by enhanced oxidative phosphorylation, and anti-inflammatory macrophages rely on oxidative phosphorylation for energy production ( 118 – 121 ). MSCs can induce anti-inflammatory macrophage polarization and promote tissue repair through metabolic reprogramming ( 122 ).…”

Section: How Mscs Regulate Macrophage Polarizationmentioning

confidence: 99%

Advances in the Regulation of Macrophage Polarization by Mesenchymal Stem Cells and Implications for ALI/ARDS Treatment

2022

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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common condition with high mortality. ALI/ARDS is caused by multiple etiologies, and the main clinical manifestations are progressive dyspnea and intractable hypoxemia. Currently, supportive therapy is the main ALI/ARDS treatment, and there remains a lack of targeted and effective therapeutic strategies. Macrophages are important components of innate immunity. M1 macrophages are pro-inflammatory, while M2 macrophages are anti-inflammatory and promote tissue repair. Mesenchymal stem cells (MSCs) are stem cells with broad application prospects in tissue regeneration due to their multi-directional differentiation potential along with their anti-inflammatory and paracrine properties. MSCs can regulate the balance of M1/M2 macrophage polarization to improve the prognosis of ALI/ARDS. In this paper, we review the mechanisms by which MSCs regulate macrophage polarization and the signaling pathways associated with polarization. This review is expected to provide new targets for the treatment of ALI/ARDS.

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The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming

Cited by 34 publications

References 195 publications

Damaged Mesenchymal Cells Dampen the Inflammatory Response of Macrophages and the Formation of Osteoclasts

Damaged Mesenchymal Cells Dampen the Inflammatory Response of Macrophages and the Formation of Osteoclasts

In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions

Advances in the Regulation of Macrophage Polarization by Mesenchymal Stem Cells and Implications for ALI/ARDS Treatment

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