CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation

Cruz, Fernanda Ferreira; Borg, Zachary D.; Goodwin, Meagan; Coffey, Amy L.; Wagner, Darcy E.; Rocco, Patrícia Rieken Macêdo; Weiss, Daniel J.

doi:10.5966/sctm.2015-0141

Cited by 28 publications

(45 citation statements)

References 80 publications

(170 reference statements)

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“…A role for PGE 2 has been demonstrated in MSC-and MAPC-mediated suppression of pathology in murine models of GVHD [53,54], while in murine models of colitis TSG-6 production is required for efficacy of BM-MSC [41]. Similarly, preclinical studies using MSC in pulmonary disorders have provided promising results [2,4,26,[55][56][57][58][59][60], with MSC therapy being associated with expansion of T reg , promotion of antiinflammatory macrophages, suppression of Th2-and Th17-associated cytokines and enhanced microbial clearance by macrophages in ARDS [45,48,61].…”

Section: Msc and Macrophages: Effects At Secondary Sitesmentioning

confidence: 99%

“…The capacity for both tissue repair and immunomodulation have led to MSC being seen as a potential cell therapy for asthma [26,[55][56][57][58]. In these studies, the therapeutic efficacy of MSC has been attributed to reduction of airway inflammation, expansion of T reg in vivo and suppression of Th2-and Th17-associated cytokines.…”

Section: Msc and Macrophages: Effects At Secondary Sitesmentioning

confidence: 99%

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The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

Carty

Mahon

English

2017

Clinical and Experimental Immunology

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SummaryMesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies. A complex crosstalk exists through which MSC and macrophages communicate, a communication that is not controlled exclusively by MSC. Here, we examine the evidence that suggests that MSC not only respond to inflammatory macrophages and adjust their secretome accordingly, but also that macrophages respond to encounters with MSC, creating a feedback loop which contributes to the immune regulation observed following MSC therapy. Future studies examining the effects of MSC on macrophages should consider the antagonistic role that macrophages play in this exchange.

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Section: Msc and Macrophages: Effects At Secondary Sitesmentioning

confidence: 99%

Section: Msc and Macrophages: Effects At Secondary Sitesmentioning

confidence: 99%

The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

Carty

Mahon

English

2017

Clinical and Experimental Immunology

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“…BMNC can also induce homeostasis in chronically inflamed tissues refractory to other treatments, such as OA‐affected joints and the respiratory system . Macrophage progenitors are the primary cells in BMNC responsible for downregulating inflammation and may, through their homeostatic effects, provide therapeutic means for restoring joint homeostasis …”

Section: Introductionmentioning

confidence: 99%

“…Bone marrow mononuclear cells (BMNC), a rich source of macrophage (>50% macrophages) and hematopoietic progenitors (~30%), are readily isolated from bone marrow aspirates. 34 Macrophages in bone marrow by default promote a regulatory response that counteracts the deleterious effects of inflammation and therefore are considered biased M2-like progenitors. 34,35 Macrophages in BMNC resolve inflammation in association with increased production of IL-10, 33,36,37 a key cytokine in chondrocyte metabolism and recovery from injury.…”

Section: Introductionmentioning

confidence: 99%

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

et al. 2020

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Synovial inflammation is a central feature of osteoarthritis (OA), elicited when local regulatory macrophages (M2‐like) become overwhelmed, activating an inflammatory response (M1‐like). Bone marrow mononuclear cells (BMNC) are a source of naïve macrophages capable of reducing joint inflammation and producing molecules essential for cartilage metabolism. This study investigated the response of BMNC to normal (SF) and inflamed synovial fluid (ISF). Equine BMNC cultured in autologous SF or ISF (n = 8 horses) developed into macrophage‐rich cultures with phenotypes similar to cells native to normal SF and became more confluent in ISF (~100%) than SF (~25%). BMNC cultured in SF or ISF were neither M1‐ nor M2‐like, but exhibited aspects of both phenotypes and a regulatory immune response, characterized by increasing counts of IL‐10+ macrophages, decreasing IL‐1β concentrations and progressively increasing IL‐10 and IGF‐1 concentrations. Changes were more marked in ISF and suggest that homeostatic mechanisms were preserved over time and were potentially favored by progressive cell proliferation. Collectively, our data suggest that intra‐articular BMNC could increase synovial macrophage counts, potentiating the macrophage‐ and IL‐10‐associated mechanisms of joint homeostasis lost during the progression of OA, preserving the production of cytokines involved in tissue repair (PGE2, IL‐10) generally impaired by frequently used corticosteroids.

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“…Due to the signaling link between the nasal cavity and bone marrow, a large number of EOS are stimulated by allergens that infiltrate local tissues (11). Bone marrow releases EOS hematopoietic progenitor cells, namely CD34-positive (CD34 + ) cells, which are targeted to various tissues and organs that then differentiate and develop into mature EOS under the control of local growth factors (12). Mature EOS produce, store and rapidly secrete diverse mediators, including cationic proteins, cytokines, chemokines and growth factors, that are important in inflammation and immune regulatory responses (13).…”

Section: Introductionmentioning

confidence: 99%

Effects of chemokine receptor 3 gene silencing by RNA interference on eosinophils

Liu

Zhu

Zhang

2016

Experimental and Therapeutic Medicine

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The present study aimed to use RNA interference (RNAi) to silence chemokine receptor 3 (CCR3) and observe the effects on eosinophils (EOS) in mice with allergic rhinitis (AR). CCR3 small interfering RNA (siRNA) lentiviral vectors were transduced into purified EOS cells cultured in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses were also used to detect the efficiency of silencing, and flow cytometry was used to detect the EOS apoptosis rates. Experimental mice were grouped for nasal administration, and the lentivirus was then dispensed to AR mice. RT-PCR and western blots were performed to detect the expression levels of CCR3 mRNA and protein in EOS extracted from bone marrow, peripheral blood and nasal mucosa. Furthermore, flow cytometry was performed to detect changes to CD34-positive (CD34+) cells in each group. The CCR3 siRNA lentiviral vector exhibited high efficiency in silencing CCR3 mRNA and protein expression, inhibited growth and promoted apoptosis of EOS. In addition, the expression of CCR3 mRNA and protein in the bone marrow, peripheral blood and nasal mucosa of mice in the CCR3 siRNA treatment group were lower than those in the control group (P<0.05), whereas the number of CD34+ cells in the CCR3 siRNA treatment group was not significantly different compared with that in the control group (P>0.05). CCR3 RNAi could effectively silence the expression of CCR3 mRNA and protein both in vitro and in vivo, thus promoting apoptosis of EOS and inhibiting its growth, migration and invasion.

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CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation

Cited by 28 publications

References 80 publications

The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

Effects of chemokine receptor 3 gene silencing by RNA interference on eosinophils

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