Immunomodulatory influence of bone marrow-derived mesenchymal stem cells on neuroinflammation in astrocyte cultures

Schäfer, Sabrina; Calas, André-Guilhem; Vergouts, Maxime; Hermans, Emmanuel

doi:10.1016/j.jneuroim.2012.04.018

Cited by 37 publications

(31 citation statements)

References 40 publications

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“…mRNA expression of the cytokines TNF alpha and IL-6 as well as of iNOS was pronouncedly induced by LPS as expected, with more increased reactivity of SOD1G93A transgenic astrocytes, and significantly down regulated by pre-incubation with MSC CM. Several studies have similarly described an altered expression of inflammatory molecules upon MSC treatment [25], [62], [63]. One must therefore conclude that this down regulation of pro-inflammatory factors is mediated via factors released by MSC.…”

Section: Discussionmentioning

confidence: 93%

“…Based on previous studies assessing MSC effects in vitro and in vivo , we therefore aimed to find out, whether expression of growth factors, cytokines and chemokines previously found to be modified by MSC and of particular interest with regard to ALS pathophysiology and therapy was influenced by MSC CM in our in vitro models [10], [12], [23], [24], [25]. Protective effects of growth factors, such as CNTF (ciliary neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), IGF-1 (insulin-like growth factor 1), FGF2 (basic fibroblast growth factor 2) and VEGF (vascular endothelial growth factor) [26], [27], [28], [29], [30] have been shown in rodent models of ALS.…”

Section: Introductionmentioning

confidence: 99%

“…Based on a previous study assessing MSC effects pro-and anti- inflammatory factors in vitro in an astrocytic cell line, we therefore investigated whether we could reproduce MSC CM-induced modification on LPS-induced production of the cytokines TNFα, IL-6 and IL-10 and of the proinflammatory enzymes iNOS and COX2 [25] and whether there were differential effects on non-transgenic compared to SOD1G93A transgenic astrocytes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS) - In Vitro Evidence from Primary Motor Neuron Cultures, NSC-34 Cells, Astrocytes and Microglia

et al. 2013

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Administration of mesenchymal stromal cells (MSC) improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice), NSC-34 cells and glial cells (astrocytes, microglia) (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice) in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM) attenuated staurosporine (STS) - induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells, we found that glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) gene expression in astrocytes were significantly enhanced by MSC CM, with differential responses of non-transgenic and mutant astrocytes. Expression of Vascular Endothelial Growth Factor (VEGF) in NSC-34 cells was significantly upregulated upon MSC CM-treatment. MSC CM significantly reduced the expression of the cytokines TNFα and IL-6 and iNOS both in transgenic and non-transgenic astrocytes. Gene expression of the neuroprotective chemokine Fractalkine (CX3CL1) was also upregulated in mutant SOD1G93A transgenic astrocytes by MSC CM treatment. Correspondingly, MSC CM increased the respective receptor, CX3CR1, in mutant SOD1G93A transgenic microglia. Our data demonstrate that MSC modulate motor neuronal and glial response to apoptosis and inflammation. MSC therefore represent an interesting candidate for further preclinical and clinical evaluation in ALS.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS) - In Vitro Evidence from Primary Motor Neuron Cultures, NSC-34 Cells, Astrocytes and Microglia

et al. 2013

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“…However, the immunomodulatory effects of MSCs on astrocytes are still limited. One study has shown that MSCs can inhibit the production of cytokines in LPS-activated astrocyte cultures, reducing not only the proinflammatory cytokines, but also the expression of the anti-inflammatory IL-10 [53]. …”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury

Zhang

Liu

et al. 2013

J Neuroinflammation

335

270

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BackgroundPrevious studies have shown beneficial effects of mesenchymal stem cell (MSC) transplantation in central nervous system (CNS) injuries, including traumatic brain injury (TBI). Potential repair mechanisms involve transdifferentiation to replace damaged neural cells and production of growth factors by MSCs. However, few studies have simultaneously focused on the effects of MSCs on immune cells and inflammation-associated cytokines in CNS injury, especially in an experimental TBI model. In this study, we investigated the anti-inflammatory and immunomodulatory properties of MSCs in TBI-induced neuroinflammation by systemic transplantation of MSCs into a rat TBI model.Methods/resultsMSCs were transplanted intravenously into rats 2 h after TBI. Modified neurologic severity score (mNSS) tests were performed to measure behavioral outcomes. The effect of MSC treatment on neuroinflammation was analyzed by immunohistochemical analysis of astrocytes, microglia/macrophages, neutrophils and T lymphocytes and by measuring cytokine levels [interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, interferon-γ, RANTES, macrophage chemotactic protein-1, macrophage inflammatory protein 2 and transforming growth factor-β1] in brain homogenates. The immunosuppression-related factors TNF-α stimulated gene/protein 6 (TSG-6) and nuclear factor-κB (NF-κB) were examined by reverse transcription-polymerase chain reaction and Western blotting. Intravenous MSC transplantation after TBI was associated with a lower density of microglia/macrophages and peripheral infiltrating leukocytes at the injury site, reduced levels of proinflammatory cytokines and increased anti-inflammatory cytokines, possibly mediated by enhanced expression of TSG-6, which may suppress activation of the NF-κB signaling pathway.ConclusionsThe results of this study suggest that MSCs have the ability to modulate inflammation-associated immune cells and cytokines in TBI-induced cerebral inflammatory responses. This study thus offers a new insight into the mechanisms responsible for the immunomodulatory effect of MSC transplantation, with implications for functional neurological recovery after TBI.

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“…Despite the fact that neuroinflammation occurs following MSC transplantation in healthy [21] and diseased [52] brain, many researchers ascribe neuroprotective effects to MSCs [90]. In vitro , MSCs have been shown to reduce the TNFα and nitric oxide production of lipopolysaccharide-stimulated microglia [91,92] and to suppress the production of pro-inflammatory cytokines in co-culture with astrocytes [93]. Therefore, the application of MSCs on their own might hold great potential as a strategy to modify neuroinflammation in vivo .…”

Section: Introductionmentioning

confidence: 99%

Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

et al. 2013

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Over the past decade a lot of research has been performed towards the therapeutic use of mesenchymal stem cells (MSCs) in neurodegenerative and neuroinflammatory diseases. MSCs have shown to be beneficial in different preclinical studies of central nervous system (CNS) disorders due to their immunomodulatory properties and their capacity to secrete various growth factors. Nevertheless, most of the transplanted cells die within the first hours after transplantation and induce a neuroinflammatory response. In order to increase the efficacy of MSC transplantation, it is thus imperative to completely characterise the mechanisms mediating neuroinflammation and cell death following MSC transplantation into the CNS. Consequently, different components of these cell death- and neuroinflammation-inducing pathways can be targeted in an attempt to improve the therapeutic potential of MSCs for CNS disorders.

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Immunomodulatory influence of bone marrow-derived mesenchymal stem cells on neuroinflammation in astrocyte cultures

Cited by 37 publications

References 40 publications

Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS) - In Vitro Evidence from Primary Motor Neuron Cultures, NSC-34 Cells, Astrocytes and Microglia

Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS) - In Vitro Evidence from Primary Motor Neuron Cultures, NSC-34 Cells, Astrocytes and Microglia

Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury

Tackling the physiological barriers for successful mesenchymal stem cell transplantation into the central nervous system

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