scholarly journals The Synergistic Anti-Apoptosis Effects of Amniotic Epithelial Stem Cell Conditioned Medium and Ponesimod on the Oligodendrocyte Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Fahimeh Safaeinejad ◽  
Sareh Asadi ◽  
Shiva Ghafghazi ◽  
Hassan Niknejad
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Combination Therapy ◽  
Conditioned Medium ◽  
Annexin V ◽  
Current Treatment ◽  
Epithelial Stem Cells ◽  
Apoptotic Effect ◽  
S1p Receptor ◽  
Anti Inflammatory

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.

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 The emergence of amnion epithelial stem cells for the treatment of Multiple Sclerosis

2011 ◽  
Vol 31 (3) ◽  
pp. 256-271 ◽  
Author(s):  
Courtney McDonald ◽  
Christopher Siatskas ◽  
Claude C.A. Bernard
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Epithelial Stem Cells

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 The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Maria Younes ◽  
Carl Ammoury ◽  
Tony Haykal ◽  
Leah Nasr ◽  
Rita Sarkis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Proliferative Effect ◽  
Apoptotic Effect

Abstract Background Herbal medicines have been a major target for numerous studies through the past years as an alternative treatment for cancer, mainly due to their minimal effects on normal healthy cells. Annona cherimola, popularly known as Cherimoya, is an edible natural fruit rich in phytochemical components and known to possess various biological activities. Previous studies have reported the anti-cancerous effect of A. cherimola ethanolic leaf extract (AELE) on leukemia. This study aims at studying the potential anti-cancer activity of this extract in vitro in two different breast cancer cell lines, namely MDA-MB-231 and MCF-7, in addition to investigating its toxicity on normal mesenchymal stem cells. Methods The anti-proliferative effect of AELE was evaluated via cell viability assay. Propidium iodide staining, Cell Death Detection ELISA and flow cytometry analysis of Annexin V binding were used to assess cell cycle progression, DNA fragmentation and apoptosis induction, respectively. Protein expression was determined via Western Blot analysis to decipher the underlying apoptotic molecular mechanism induced upon AELE treatment. Results The anti-proliferative effect of the extract was found to be selective on the triple-negative breast cancer cell line (MDA-MB-231) in a time- and dose-dependent manner with an IC50 of 390.2 μg/mL at 48 h, with no cytotoxic effects on normal murine mesenchymal stem cells. The pro-apoptotic effect was confirmed by the increase in cellular and DNA fragmentation, flipping of the phosphatidylserine moiety to the outer leaflet, and the increase in Annexin V binding. The underlying molecular mechanism revealed the involvement of the mitochondrial pathway, as shown by alterations in mitochondrial permeability and the upregulation of cytochrome c expression. Conclusion All the data presented in our study suggest that AELE exhibits a selective anti-proliferative and pro-apoptotic effect on the chemo-resistant MDA-MB-231 breast cancer cells, providing evidence for the anti-tumor effects of A. cherimola.

scholarly journals Inhibition of Pro-Inflammatory Cytokines by Metabolites of Streptomycetes—A Potential Alternative to Current Anti-Inflammatory Drugs?

2020 ◽  
Vol 8 (5) ◽  
pp. 621
Author(s):  
Jiří Hrdý ◽  
Lenka Súkeníková ◽  
Petra Petrásková ◽  
Olga Novotná ◽  
David Kahoun ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Current Treatment ◽  
Attractive Alternative ◽  
Anti Cancer ◽  
Dependent Inhibition ◽  
Apoptotic Effect ◽  
Potential Alternative ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Drug Leads

Current treatment of chronic diseases includes, among others, application of cytokines, monoclonal antibodies, cellular therapies, and immunostimulants. As all the underlying mechanisms of a particular diseases are not always fully clarified, treatment can be inefficient and associated with various, sometimes serious, side effects. Small secondary metabolites produced by various microbes represent an attractive alternative as future anti-inflammatory drug leads. Compared to current drugs, they are cheaper, can often be administered orally, but still can keep a high target-specificity. Some compounds produced by actinomycetes or fungi have already been used as immunomodulators—tacrolimus, sirolimus, and cyclosporine. This work documents strong anti-inflammatory features of another secondary metabolite of streptomycetes—manumycin-type polyketides. We compared the effect of four related compounds: manumycin A, manumycin B, asukamycin, and colabomycin E on activation and survival of human monocyte/macrophage cell line THP-1. The anti-cancer effect of manucycine A has been demonstrated; the immunomodulatory capacities of manumycin A are obvious when using micromolar concentrations. The application of all four compounds in 0.25–5 μM concentrations leads to efficient, concentration-dependent inhibition of IL-1β and TNF expression in THP-1 upon LPS stimulation, while the three latter compounds show a significantly lower pro-apoptotic effect than manumycin A. We have demonstrated the anti-inflammatory capacity of selected manumycin-type polyketides.

scholarly journals Synergistic Inhibitory Effect of Human Umbilical Cord Matrix Mesenchymal Stem Cells-Conditioned Medium and Atorvastatin on MCF7 Cancer Cells Viablity and Migration

2021 ◽  
Author(s):  
Reyhaneh Abolghasemi ◽  
Somayeh Ebrahimi-barough ◽  
Jafar Ai
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Annexin V ◽  
Treated Group ◽  
Human Umbilical Cord ◽  
Umbilical Cord Matrix ◽  
Combination Treated Group

Abstract Background: Tumor growth and metastasis eventuate from an interaction between cancer cells and the surrounding extracellular matrix. Recent studies demonstrated inhibitory effects of mesenchymal stem cells on breast tumors. Likewise, the emerging interest in statins as anticancer agents is based on their pleiotropic effects. In the present study, we investigated whether atorvastatin and umbilical cord matrix derived mesenchymal stem cells-conditioned medium alone and combined with each other affect the MCF7 cancer cells viability and interactions.Methods: We measured the viability, apoptosis, and necrosis of MCF7 by MTT assay, Annexin-V/PI staining by flow cytometry, and quantitative real-time PCR. Two-dimensional culture and hanging drop aggregation assay illustrated the morphological changes in single cancer cells and spheroid configuration respectively. We traced the MCF7 migration via scratch-wound healing and trans-well assays. Results: The results showed inhibition of cancer cell viability in all treated groups compared with the control group, but the effect of atorvastatin and conditioned medium combination was further than each one alone. Cancer cells shrinkage and chromatin condensation in the inverted light microscopy and fluorescent staining microscopy indicated apoptosis in treated cells. The annexin V/PI analysis especially in the combination-treated group displayed decreasing in DNA synthesis and cell cycle arrest. The mRNA expressions of caspases 3, 8, 9, and Bcl-2 genes were along with extrinsic and intrinsic apoptosis pathways. Conditioned medium disrupts the connections between cancer cells in the three-dimensional spheroids configuration. The migration of treated cells across the wound area and trans-well diminished, particularly in the combination-treated group. Conclusions: For the first time, the synergistic anti-proliferative and anti-motility effect of atorvastatin along with human umbilical cord mesenchymal stem cells-derived conditioned medium on MCF7 breast cancer cells have been proved. These findings point to some new therapeutic strategies with a focus on the crosstalk between breast cancer cells and microenvironment.

199 EFFECTS OF REPROGRAMMING-CONDITIONED MEDIUM ON ULTRAVIOLET RAY A–DAMAGED HUMAN DERMAL FIBROBLASTS

2017 ◽  
Vol 29 (1) ◽  
pp. 208
Author(s):  
J. Kang ◽  
S. G. Lee ◽  
J. H. Kang ◽  
S.-M. Park ◽  
S. Y. Heo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Conditioned Medium ◽  
Pluripotent Stem Cells ◽  
Annexin V ◽  
Hierarchical Cluster ◽  
Stem Cell Differentiation ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
Ultraviolet Ray

Ultraviolet ray A (UVA) is an electromagnetic light with a long wavelength from the sun. The penetration of UVA deep into the human dermis causes changes in cells, such as DNA fragmentation, apoptosis, and senescence, eventually leading a decline of proliferation and wound-healing ability. These changes induced by UVA exposure are similar to those seen in the process of stem cell differentiation. We postulated that the condition that reverses cellular differentiation may alleviate the UVA-induced damage in skin cells. Human dermal fibroblasts (HDF) could be reprogrammed to induced pluripotent stem cells (iPSC). Conditioned medium (CM) was prepared during the process of iPSC reprogramming (referred to as Repro-CM). The UVA-irradiated HDF were cultured in Repro-CM for 24 h. In comparison with CM prepared from the culture of normal HDF and iPSC (referred to as HDF-CM and iPSC-CM, respectively), effects of Repro-CM on UVA-irradiated cells were investigated. Viability, wound-healing ability, apoptosis, and senescence of HDF were analysed by WST-1 assay, scratch assay, Annexin V assay, and senescence-associated β-galactosidase assay, respectively. Upon recovering from the UVA-induced damage, viability and wound-healing ability of HDF were significantly different (P < 0.05) among the treatments in the order of Repro-, HDF-, and iPSC-CM. In the same context, apoptosis and senescence were significantly different (P < 0.05) in the order of iPSC-, HDF-, and Repro-CM. Interestingly, iPSC-CM did not substantially ameliorate UVA-induced damage, suggesting that the conditions optimized to pluripotent stem cells may not be suitable for the recovery from damage in terminally differentiated cells, such as fibroblasts. The RNA-seq analysis was performed to assess the genome-wide transcriptional profile in the process of recovery. Repro- and HDF-CM were categorized more closely than iPSC-CM in hierarchical cluster analysis. In comparison with iPSC-CM, the up-regulated genes by Repro-CM treatment were related to regulation of cell proliferation and cell metabolism, whereas down-regulated genes were related to antiapoptosis and response to stimulation of chemical and organic substances. Overall, providing an environment of reprogramming, as shown by Repro-CM in the present study, may assist recovery of HDF from UVA-induced damage. The results of the study may be applicable in developing pharmaceuticals to treat aging and wrinkling of the skin caused by UVA irradiation.

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