Anti-inflammatory Effects of Conditioned Medium of Periodontal Ligament Derived Stem Cells on Chondrocytes, Synoviocytes and Meniscus Cells

Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system. The current treatment of Multiple sclerosis is based on anti-inflammatory disease-modifying treatments, which can not regenerate myelin and eventually neurons. So, we need new approaches for axonal protection and remyelination. Amniotic epithelial stem cells amniotic epithelial cells, as a neuroprotective and neurogenic agent, are a proper source in tissue engineering and regenerative medicine. Due to differentiation capability and secretion of growth factors, AECs can be a candidate for the treatment of MS. Moreover, sphingosine-1-phosphate (S1P) receptor modulators were recently approved by FDA for MS. Ponesimod is an S1P receptor-1 modulator that acts selectively as an anti-inflammatory agent and provides a suitable microenvironment for the function of the other neuroprotective agents. In this study, due to the characteristics of AECs, they are considered a treatment option in MS. The conditioned medium of AECs concurrently with ponesimod was used to evaluate the viability of the oligodendrocyte cell line after induction of cell death by cuprizone. Cell viability after treatment by conditioned medium and ponesimod was increased compared to untreated groups. Also, the results showed that combination therapy with CM and ponesimod had a synergistic anti-apoptotic effect on oligodendrocyte cells. The combination treatment with CM and ponesimod reduced the expression of caspase-3, caspase-8, Bax, and Annexin V proteins and increased the relative BCL-2/Bax ratio, indicating inhibition of apoptosis as a possible mechanism of action. Based on these promising results, combination therapy with amniotic stem cells and ponesimode could be a proper alternative for multiple sclerosis treatment.

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Conditioned medium from human gingival mesenchymal stem cells protects motor-neuron-like NSC-34 cells against scratch-injury-induced cell death

International Journal of Immunopathology and Pharmacology ◽

10.1177/0394632017740976 ◽

2017 ◽

Vol 30 (4) ◽

pp. 383-394 ◽

Cited By ~ 10

Author(s):

Thangavelu Soundara Rajan ◽

Francesca Diomede ◽

Placido Bramanti ◽

Oriana Trubiani ◽

Emanuela Mazzon

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Cell Death ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Motor Neuron ◽

Conditioned Medium ◽

Caspase 3 ◽

Tnf Α ◽

Anti Inflammatory

Neuronal cell death is a normal process during central nervous system (CNS) development and is also involved in the death of motor neurons in diverse spinal motor neuron degenerative diseases. Here, we investigated the neuroprotective effect of secretory factors released from human gingival mesenchymal stem cells (hGMSCs) in mechanically injured murine motor-neuron-like NSC-34 cells. The cells were exposed to scratch injury and the markers for apoptosis and oxidative stress were examined. Immunocytochemistry results showed that proapoptotic markers cleaved caspase-3 and Bax were elevated while anti-apoptotic protein Bcl-2 was suppressed in scratch-injured NSC-34 cells. Oxidative stress markers SOD-1, inducible nitric oxide synthase (iNOS), Cox-2, and proinflammatory cytokine tumor necrosis factor alpha (TNF-α) were activated. Conditioned medium (CM) derived from hGMSCs (hGMSC-CM) significantly blocked the cell death by suppressing SOD-1, iNOS, TNF-α, cleaved caspase-3, and Bax. Bcl-2 and anti-inflammatory cytokine anti-interleukin 10 (IL-10) were increased in hGMSC-CM-treated injured cells. Moreover, hGMSC-CM treatment upregulated neurotrophins anti-brain-derived neurotrophic factor (BDNF) and NT3. Western blot data of hGMSC-CM revealed the presence of neurotrophins nerve growth factor (NGF), NT3, anti-inflammatory cytokines IL-10, and transforming growth factor beta (TGF-β), suggesting their positive role to elicit neuroprotection. Our results propose that hGMSC-CM may serve as a simple and potential autologous therapeutic tool to treat motor neuron injury.

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Enhancement of Anti-Inflammatory and Osteogenic Abilities of Mesenchymal Stem Cells via Cell-to-Cell Adhesion to Periodontal Ligament-Derived Fibroblasts

Stem Cells International ◽

10.1155/2017/3296498 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Keita Suzuki ◽

Naoyuki Chosa ◽

Shunsuke Sawada ◽

Naoki Takizawa ◽

Takashi Yaegashi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Inflammatory Cytokines ◽

Periodontal Ligament ◽

Direct Contact ◽

Cell Types ◽

Stem Cell Markers ◽

Periodontal Ligament Fibroblasts ◽

Anti Inflammatory ◽

Inflammatory Tissue

Mesenchymal stem cells (MSCs) are involved in anti-inflammatory events and tissue repair; these functions are activated by their migration or homing to inflammatory tissues in response to various chemokines. However, the mechanism by which MSCs interact with other cell types in inflammatory tissue remains unclear. We investigated the role of periodontal ligament fibroblasts (PDL-Fs) in regulating the anti-inflammatory and osteogenic abilities of bone marrow-derived- (BM-) MSCs. The expression of monocyte chemotactic protein- (MCP-)1 was significantly enhanced by stimulation of PDL-Fs with inflammatory cytokines. MCP-1 induced the migratory ability of BM-MSCs but not PDL-Fs. Expression levels of anti-inflammatory and inflammatory cytokines were increased and decreased, respectively, by direct-contact coculture between MSCs and PDL-Fs. In addition, the direct-contact coculture enhanced the expression of MSC markers that play important roles in the self-renewal and maintenance of multipotency of MSCs, which in turn induced the osteogenic ability of the cells. These results suggest that MCP-1 induces the migration and homing of BM-MSCs into the PDL inflammatory tissue. The subsequent adherence of MSCs to PDL-Fs plays an immunomodulatory role to terminate inflammation during wound healing and upregulates the expression stem cell markers to enhance the stemness of MSCs, thereby facilitating bone formation in damaged PDL tissue.

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The Potential Safe Antifibrotic Effect of Stem Cell Conditioned Medium and Nilotinib Combined Therapy by Selective Elimination of Rat Activated HSCs

BioMed Research International ◽

10.1155/2021/6678913 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Ahmed Nabil ◽

Koichiro Uto ◽

Faten Zahran ◽

Reham Soliman ◽

Ayman A. Hassan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Cell Lines ◽

Hepatic Stellate Cells ◽

Normal Cell ◽

Combined Therapy ◽

Stellate Cells ◽

Collagen Deposition ◽

Anti Inflammatory

Hepatic fibrosis is a progressive disease with serious clinical complications that arise from abnormal propagation and activation of multiple inflammatory pathways. Nilotinib is an oral tyrosine kinase inhibitor with antifibrotic activity. Mesenchymal stem cells (MSCs) are blank cells and can differentiate into specific cell types. They have the potential to repair and regenerate cells. MSCs have a special paracrine fashion where they produce special exosomes, microvesicles, and cytokines like IL-6, transforming growth factor-beta (TGF-β), and HGF as well as hepatic stellate cell suppressors. This paracrine fashion can decrease collagen deposition, enhance antifibrotic, anti-inflammatory, and angiogenic activity in vitro and in vivo. In our study, the rat’s hepatic stellate cells (HSCs) in addition to different normal cell lines were treated with Nilotinib alone and in combination with liver mesenchymal stem cells conditioned medium (LMSCs-CM) for 24 h. Mono and combined therapy antifibrotic and cytotoxicity effects were evaluated using different parameters including α-SMA, cytochrome c, P53 expression, collagen deposition, DNA content, oxidative stress parameters, cell viability, and apoptosis by flow cytometry analysis. Our results showed that Nilotinib and LMSCs-CM in combination had a significantly potent antifibrotic and anti-inflammatory effect on activated hepatic stellate cells than Nilotinib alone; otherwise, this combination showed the best safety with minimal cytotoxicity on different normal cell lines.

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Conditioned Medium from Periodontal Ligament Stem Cells Enhances Periodontal Regeneration

Tissue Engineering Part A ◽

10.1089/ten.tea.2016.0274 ◽

2017 ◽

Vol 23 (9-10) ◽

pp. 367-377 ◽

Cited By ~ 34

Author(s):

Mizuki Nagata ◽

Kengo Iwasaki ◽

Keiko Akazawa ◽

Motohiro Komaki ◽

Naoki Yokoyama ◽

...

Keyword(s):

Stem Cells ◽

Conditioned Medium ◽

Periodontal Ligament ◽

Periodontal Regeneration ◽

Periodontal Ligament Stem Cells

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Conditioned Medium of Mesenchymal Stem Cells Pulsed with Theobromine Can Instruct Anti-Inflammatory Neutrophils

Zahedan Journal of Research in Medical Sciences ◽

10.5812/zjrms.86967 ◽

2020 ◽

Vol 22 (2) ◽

Author(s):

Seyyed Meysam Abtahi Froushani ◽

Ardeshir Abbasi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Wistar Rats ◽

Phosphodiesterase Inhibitor ◽

Neutral Red ◽

Myeloperoxidase Activity ◽

Oxygen Species ◽

Differentiation Potential ◽

Anti Inflammatory

Background: Both adenosine signaling and phosphodiesterase inhibitor agents can alter the survivability and differentiation potential of Mesenchymal Stem Cells (MSCs). On the other hand, the crosstalk between MSCs and immunocytes like neutrophils is clear. Objectives: Here, we examined the consequence of inflammatory functions of neutrophils after co-culture with conditioned MSC Medium (CM) whose MSCs had previously been pulsed with theobromine. Methods: Mesenchymal stem cells were separated and characterized by the bone marrow of Wistar rats. These cells were primed with different concentrations of theobromine (0, 10, 50, and 100 μM) for 48 hours. Neutrophils were primed with CM for four hours and their performance was examined. Results: CM primed with theobromine at low to moderate concentrations protected the neutral red removal by neutrophils and potentiated CM potential to support neutrophils from apoptosis. CM from MSC primed with theobromine augmented the phagocytosis potential of co-cultured neutrophils. Conversely, CM isolated from MSCs pulsed with theobromine reduced the production of potentially noxious reactive oxygen species and myeloperoxidase activity more profoundly than did CM from un-pulsed MSCs. Conclusions: Conditioned medium of MSCs pulsed with theobromine can instruct anti-inflammatory neutrophils.

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Hypoxic Preconditioning Enhances the Efficacy of Mesenchymal Stem Cells-Derived Conditioned Medium in Switching Microglia toward Anti-inflammatory Polarization in Ischemia/Reperfusion

Cellular and Molecular Neurobiology ◽

10.1007/s10571-020-00868-5 ◽

2020 ◽

Author(s):

Han Yu ◽

Zhihong Xu ◽

Gaojing Qu ◽

Huimin Wang ◽

Lulu Lin ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Ischemia Reperfusion ◽

Hypoxic Preconditioning ◽

Anti Inflammatory

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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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