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

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.

scholarly journals Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity

2020 ◽  
Vol 9 (9) ◽  
pp. 2913
Author(s):  
Ji Yeon Kang ◽  
Mi-Kyung Oh ◽  
Hansol Joo ◽  
Hyun Sung Park ◽  
Dong-Hoon Chae ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Experimental Colitis ◽  
Wharton’S Jelly ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Wharton's Jelly ◽  
Indoleamine 2,3 Dioxygenase ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory

The therapeutic applications of mesenchymal stem cells (MSCs) have been actively explored due to their broad anti-inflammatory and immunomodulatory properties. However, the use of xenogeneic components, including fetal bovine serum (FBS), in the expansion media might pose a risk of xenoimmunization and zoonotic transmission to post-transplanted patients. Here, we extensively compared the physiological functions of human Wharton’s jelly-derived MSCs (WJ-MSCs) in a xeno-free medium (XF-MSCs) and a medium containing 10% FBS (10%-MSCs). Both groups showed similar proliferation potential; however, the 10%-MSCs showed prolonged expression of CD146, with higher colony-forming unit-fibroblast (CFU-F) ability than the XF-MSCs. The XF-MSCs showed enhanced adipogenic differentiation potential and sufficient hematopoietic stem cell (HSC) niche activity, with elevated niche-related markers including CXCL12. Furthermore, we demonstrated that the XF-MSCs had a significantly higher suppressive effect on human peripheral blood-derived T cell proliferation, Th1 and Th17 differentiation, as well as naïve macrophage polarization toward an M1 phenotype. Among the anti-inflammatory molecules, the production of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase 2 (NOS2) was profoundly increased, whereas cyclooxygenase-2 (COX-2) was decreased in the XF-MSCs. Finally, the XF-MSCs had an enhanced therapeutic effect against mouse experimental colitis. These findings indicate that xeno-free culture conditions improved the immunomodulatory properties of WJ-MSCs and ex vivo-expanded XF-MSCs might be an effective strategy for preventing the progression of colitis.

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

2017 ◽  
Vol 30 (4) ◽  
pp. 383-394 ◽  
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.

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

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.

scholarly journals Human Glioblastoma-Derived Mesenchymal Stem Cell to Pericytes Transition and Angiogenic Capacity in Glioblastoma Microenvironment

2018 ◽  
Vol 46 (1) ◽  
pp. 279-290 ◽  
Author(s):  
Dongye Yi ◽  
Wei Xiang ◽  
Qing Zhang ◽  
Yongcun Cen ◽  
Qing Su ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Blue Staining ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
And Migration ◽  
Proliferation And Migration ◽  
Vascular Formation

Background/Aims: Tumor vascular formation and maintenance are crucial events in glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to differentiate into pericytes and contribute to neovascularization in the glioma microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb-MSCs), which consist of CD90-MSCs and CD90+MSCs, are a subpopulation of MSCs that are more active in glioma vascularization. However, the functions of gb-MSCs and the microRNA (miRNA) modifications in the glioblastoma microenvironment have not yet been fully elucidated. Here, we focus on the pericyte differentiation potential of gb-MSCs and miRNA modifications in gb-MSCs during new vascular formation and glioblastoma growth. Methods: In vitro, surface markers of gb-MSCs were detected by flow cytometry; the differentiation potential was evaluated by Oil Red O staining, Alizarin Red staining and Alcian blue staining; the proliferation and migration of gb-MSCs in different conditioned media were analyzed by the cck8 test and wound-healing assay, respectively; gb-MSC to pericyte transition was detected by immunofluorescence staining and western blot assay; angiogenetic capacity was analyzed by tube formation assay; and levels of cytokines in different supernatant were determined by ELISA. Additionally, RNA was isolated from gb-MSCs, and miRNA modifications were analyzed using the RAffymetrix miRNA microarray Results: We showed that glioblastoma-conditioned medium increased gb-MSC proliferation and migration and was capable of inducing gb-MSC differentiation into pericytes. Glioblastoma secreted angiogenic factors and gb-MSCs incubated in malignant glioblastoma-conditioned medium formed more tube-like structures, and these cells also adhered to tube-like vessels formed by human umbilical vein endothelial cells (HUVECs) on Matrigel to maintain tumor vascular structure in vitro. miRNA expression were also modified in gb-MSCs cultured in malignant glioblastoma-conditioned medium in vitro. Conclusion: These results provide new insight into the functional effects of a subpopulation of MSCs in glioblastoma and may help in the development of novel therapies for solid tumors.

scholarly journals Differentiation of Mesenchymal Stem Cells from Human Umbilical Cord Tissue into Odontoblast-Like Cells Using the Conditioned Medium of Tooth Germ CellsIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Tian Xia Li ◽  
Jie Yuan ◽  
Yan Chen ◽  
Li Jie Pan ◽  
Chun Song ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Tooth Germ ◽  
Wharton’S Jelly ◽  
Human Umbilical Cord ◽  
Differentiation Potential ◽  
Wharton's Jelly ◽  
Umbilical Cord Tissue

The easily accessible mesenchymal stem cells in the Wharton's jelly of human umbilical cord tissue (hUCMSCs) have excellent proliferation and differentiation potential, but it remains unclear whether hUCMSCs can differentiate into odontoblasts. In this study, mesenchymal stem cells were isolated from the Wharton's jelly of human umbilical cord tissue using the simple method of tissue blocks culture attachment. UCMSC surface marker expression was then evaluated for the isolated cells using flow cytometry. The third-passage hUCMSCs induced by conditioned medium from developing tooth germ cells (TGC-CM) displayed high alkaline phosphatase (ALP) levels (P<0.001), an enhanced ability to proliferate (P<0.05), and the presence of mineralized nodules. These effects were not observed in cells treated with regular medium. After induction of hUCMSCs, the results of reverse transcriptional polymerase chain reaction (PCR) indicated that the dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) genes were significantly tested. Additionally, dentin sialoprotein (DSP) and DMP1 demonstrated significant levels of staining in an immunofluorescence analysis. In contrast, the control cells failed to display the characteristics of odontoblasts. Taken together, these results suggest that hUCMSCs can be induced to differentiate into odontoblast-like cells with TGC-CM and provide a novel strategy for tooth regeneration research.

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

2018 ◽  
Vol 47 (1) ◽  
pp. 11-25 ◽  
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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