scholarly journals Acute Hypoxic Stress Affects Migration Machinery of Tissue O2-Adapted Adipose Stromal Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Olga O. Udartseva ◽  
Margarita V. Lobanova ◽  
Elena R. Andreeva ◽  
Sergey V. Buravkov ◽  
Irina V. Ogneva ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Leading Edge ◽  
Cell Stiffness ◽  
Hypoxic Exposure ◽  
Hypoxic Stress ◽  
Short Term ◽  
Migration Assays ◽  
Stromal Stem Cells

The ability of mesenchymal stromal (stem) cells (MSCs) to be mobilised from their local depot towards sites of injury and to participate in tissue repair makes these cells promising candidates for cell therapy. Physiological O2tension in an MSC niche in vivo is about 4–7%. However, most in vitro studies of MSC functional activity are performed at 20% O2. Therefore, this study focused on the effects of short-term hypoxic stress (0.1% O2, 24 h) on adipose tissue-derived MSC motility at tissue-related O2level. No significant changes in integrin expression were detected after short-term hypoxic stress. However, O2deprivation provoked vimentin disassembly and actin polymerisation and increased cell stiffness. In addition, hypoxic stress induced the downregulation ofACTR3, DSTN, MACF1, MID1, MYPT1, NCK1, ROCK1, TIAM1, andWASF1expression, the products of which are known to be involved in leading edge formation and cell translocation. These changes were accompanied by the attenuation of targeted and nontargeted migration of MSCs after short-term hypoxic exposure, as demonstrated in scratch and transwell migration assays. These results indicate that acute hypoxic stress can modulate MSC function in their native milieu, preventing their mobilisation from sites of injury.

scholarly journals Crosstalk of Endothelial and Mesenchymal Stromal Cells under Tissue-Related O2

2021 ◽  
Vol 1 (2) ◽  
pp. 116-136
Author(s):  
Olga Zhidkova ◽  
Elena Andreeva ◽  
Mariia Ezdakova ◽  
Ludmila Buravkova
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Reciprocal Effects ◽  
Hypoxic Stress ◽  
Protective Effects ◽  
Short Term ◽  
Tnf Α ◽  
Vitro Analysis ◽  
In Vitro Analysis

Mesenchymal stromal cells (MSCs) are considered a valuable tool for cell therapy. After systemic administration, the outcome of MSCs and endothelial cells (ECs) interactions strongly depend on the local microenvironment and tissue O2 levels in particular. In vitro analysis of EC effects on MSC regenerative potential in co-culture was performed after short-term interaction at “physiological” hypoxia (5% O2) and acute hypoxic stress (0.1% O2). At 5% O2, MSCs retained stromal phenotype and CFU-f numbers, osteogenic RUNX2 was upregulated. A shift in the expression of adhesion molecules, and an increase in transcription/synthesis of IL-6, IL-8 contributed to facilitation of directed migration of MSCs. In the presence of MSCs, manifestations of oxidative stress in ECs were attenuated, and a decrease in adhesion of PBMCs to TNF-α-activated ECs was observed. Under 0.1% O2, reciprocal effects of ECs and MSCs were similar to those at 5% O2. Meanwhile, upregulation of RUNX2 was canceled, IL-6 decreased, and IL-8 significantly increased. “Protective” effects of MSCs on TNF-α-ECs were less pronounced, manifested as NOS3 downregulation and intracellular NO elevation. Therefore, interaction with ECs at “physiological” hypoxia enhanced pro-regenerative capacities of MSCs including migration and anti-inflammatory modulation of ECs. Under acute hypoxic stress, the stimulating effects of ECs on MSCs and the “protective” potential of MSCs towards TNF-α-ECs were attenuated.

scholarly journals The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3491
Author(s):  
Haruka Omori ◽  
Qiusheng Shan ◽  
Kiyofumi Takabatake ◽  
Keisuke Nakano ◽  
Hotaka Kawai ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bioinformatics Analyses ◽  
Invasion And Migration ◽  
Migration Assays ◽  
Tumor Parenchyma ◽  
And Migration

Normal stromal cells surrounding the tumor parenchyma, such as the extracellular matrix (ECM), normal fibroblasts, mesenchymal stromal cells, and osteoblasts, play a significant role in the progression of cancers. However, the role of gingival and periodontal ligament tissue-derived stromal cells in OSCC progression is unclear. In this study, the effect of G-SCs and P-SCs on the differentiation, proliferation, invasion, and migration of OSCC cells in vitro was examined by Giemsa staining, Immunofluorescence (IF), (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS), invasion, and migration assays. Furthermore, the effect of G-SCs and P-SCs on the differentiation, proliferation, and bone invasion by OSCC cells in vivo was examined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Finally, microarray data and bioinformatics analyses identified potential genes that caused the different effects of G-SCs and P-SCs on OSCC progression. The results showed that both G-SCs and P-SCs inhibited the differentiation and promoted the proliferation, invasion, and migration of OSCC in vitro and in vivo. In addition, genes, including CDK1, BUB1B, TOP2A, DLGAP5, BUB1, and CCNB2, are probably involved in causing the different effects of G-SCs and P-SCs on OSCC progression. Therefore, as a potential regulatory mechanism, both G-SCs and P-SCs can promote OSCC progression.

scholarly journals Short-Term Protocols to Obtain Insulin-Producing Cells from Rat Adipose Tissue: Signaling Pathways and In Vivo Effect

2019 ◽  
Vol 20 (10) ◽  
pp. 2458 ◽  
Author(s):  
Krista Minéia Wartchow ◽  
Letícia Rodrigues ◽  
Lucas Zingano Suardi ◽  
Barbara Carolina Federhen ◽  
Nicholas Guerini Selistre ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Stromal Cells ◽  
Mapk Pathway ◽  
Activin A ◽  
Diabetic Rats ◽  
Short Term ◽  
Adipose Derived Stromal Cells ◽  
Rat Adipose Tissue

Studies using mesenchymal stromal cells (MSCs) as a source of insulin-secreting cells (IPCs) are a promising path in the pursuit for diabetes therapy. Here, we investigate three short-term differentiation protocols in order to generate IPCs from autologous adipose-derived stromal cells (ADSCs) with an expressive insulin-secreting profile in vitro and in vivo, as well as the signaling pathways involved in the chosen differentiation protocols. We extracted and cultured ADSCs and differentiated them into IPCs, using three different protocols with different inductors. Afterwards, the secretory profile was analyzed and IPCs differentiated in exendin-4/activin A medium, which presented the best secretory profile, was implanted in the kidney subcapsular region of diabetic rats. All protocols induced the differentiation, but media supplemented with exendin-4/activin A or resveratrol induced the expression and secretion of insulin more efficiently, and only the exendin-4/activin-A-supplemented medium generated an insulin secretion profile more like β-cells, in response to glucose. The PI3K/Akt pathway seems to play a negative role in IPC differentiation; however, the differentiation of ADSCs with exendin-4/activin A positively modulated the p38/MAPK pathway. Resveratrol medium activated the Jak/STAT3 pathway and generated IPCs apparently less sensitive to insulin and insulin-like receptors. Finally, the implant of IPCs with the best secretory behavior caused a decrease in hyperglycemia after one-week implantation in diabetic rats. Our data provide further information regarding the generation of IPCs from ADSCs and strengthen evidence to support the use of MSCs in regenerative medicine, specially the use of exendin-4/activin A to produce rapid and effectively IPCs with significant in vivo effects.

scholarly journals Adipose-derived stromal cells modulating composite allotransplant survival is correlated with B cell regulation in a rodent hind-limb allotransplantation model

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chien-Chang Chen ◽  
Rong-Fu Chen ◽  
Jheng-Syuan Shao ◽  
Yun-Ting Li ◽  
Yu-Chi Wang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Stromal Cells ◽  
Hind Limb ◽  
Cell Regulation ◽  
Allograft Survival ◽  
Short Term ◽  
Immunoregulatory Cytokines

Abstract Background Our previous studies demonstrated that adipose-derived mesenchymal stromal cells (ASCs) have immunomodulatory effects that prolong allograft survival in a rodent hind-limb allotransplant model. In this study, we investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation. Methods B cells isolated from splenocytes were cocultured with ASCs harvested from adipose tissue from rodent groin areas for in vitro experiments. In an in vivo study, hind-limb allotransplantation from Brown-Norway to Lewis rats was performed, and rats were treated with ASCs combined with short-term treatment with anti-lymphocyte serum (ALS)/cyclosporine (CsA) as immunosuppressants. Peripheral blood and transplanted tissue were collected for further analysis. Result An in vitro study revealed that ASCs significantly suppressed lipopolysaccharide-activated B cell proliferation and increased the percentage of Bregs. The levels of immunoregulatory cytokines, such as TGF-β1 and IL-10, were significantly increased in supernatants of stimulated B cells cocultured with ASCs. The in vivo study showed that treatment with ASCs combined with short-term ALS/CsA significantly reduced the B cell population in alloskin tissue, increased the proportion of circulating CD45Ra+/Foxp3+ B cells, and decreased C4d expression in alloskin. Conclusion ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.

EFFECT OF MULTIPOTENT MESENCHYMAL STROMAL CELLS ON THE FUNCTIONAL ACTIVITY OF MONOCYTE-DERIVED MACROPHAGES UNDER A SHORT-TERM HYPOXIC STRESS IN VITRO

2021 ◽  
Vol 55 (5) ◽  
pp. 45-52
Author(s):  
O.Yu. Alekseeva ◽  
◽  
P.I. Bobyleva ◽  
E.R. Andreeva ◽  
◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Functional Activity ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Hypoxic Stress ◽  
Hypoxic Conditions ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

We studied interactions of mesenchymal stromal cells (MSCs) and cells from the monocyte-macrophage group (MN/MP) important in the MSCs mediated therapeutic action in vivo, their anti-inflammatory and immunomodulating properties. The MSCs effect on the MN/MP functional activity was evaluated after a 6-d co-culture in standard conditions (20 % О2) and ensuing exposure of one part of MN/MP and MN/MP+MSCs to a long-term hypoxic stress (1 % О2, 24 hrs) while the other part remained at 20 % О2. As in the normal, so hypoxic conditions the MSCs stromal activity contributed to the MN/MP viability by decreasing the numbers of MN/MP cells during early apoptosis. The paracrine interaction in 20 % О2 occurred with an elevated MN/MP phagocytic activity without influence on the lysosomal compartment activity. The hypoxic stress affected the MSCs-induced phagocytic ability and activity of lysosomes. Interaction with MSCs leads to formation of a MN/MP anti-inflammatory phenotype that unveils the phagocytic potential in the presence of MSCs despite the oxygen deprivation.

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

Case study in 21 st century ecotoxicology: using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish

2020 ◽  
Author(s):  
Daniel L. Villeneuve ◽  
Brett R. Blackwell ◽  
Jenna E. Cavallin ◽  
Wan‐Yun Cheng ◽  
David J. Feifarek ◽  
...  
Keyword(s):  
Adult Female ◽  
Female Fish ◽  
Aromatase Inhibition ◽  
Short Term ◽  
Inhibition Data

scholarly journals Reovirus-induced cell-mediated immunity for the treatment of multiple myeloma within the resistant bone marrow niche

2021 ◽  
Vol 9 (3) ◽  
pp. e001803
Author(s):  
Louise M E Müller ◽  
Gemma Migneco ◽  
Gina B Scott ◽  
Jenny Down ◽  
Sancha King ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Immune Responses ◽  
Stromal Cells ◽  
Tumor Burden ◽  
Effector Memory ◽  
In Vivo Model ◽  
Bm Niche

BackgroundMultiple myeloma (MM) remains an incurable disease and oncolytic viruses offer a well-tolerated addition to the therapeutic arsenal. Oncolytic reovirus has progressed to phase I clinical trials and its direct lytic potential has been extensively studied. However, to date, the role for reovirus-induced immunotherapy against MM, and the impact of the bone marrow (BM) niche, have not been reported.MethodsThis study used human peripheral blood mononuclear cells from healthy donors and in vitro co-culture of MM cells and BM stromal cells to recapitulate the resistant BM niche. Additionally, the 5TGM1-Kalw/RijHSD immunocompetent in vivo model was used to examine reovirus efficacy and characterize reovirus-induced immune responses in the BM and spleen following intravenous administration. Collectively, these in vitro and in vivo models were used to characterize the development of innate and adaptive antimyeloma immunity following reovirus treatment.ResultsUsing the 5TGM1-Kalw/RijHSD immunocompetent in vivo model we have demonstrated that reovirus reduces both MM tumor burden and myeloma-induced bone disease. Furthermore, detailed immune characterization revealed that reovirus: (i) increased natural killer (NK) cell and CD8+ T cell numbers; (ii) activated NK cells and CD8+ T cells and (iii) upregulated effector-memory CD8+ T cells. Moreover, increased effector-memory CD8+ T cells correlated with decreased tumor burden. Next, we explored the potential for reovirus-induced immunotherapy using human co-culture models to mimic the myeloma-supportive BM niche. MM cells co-cultured with BM stromal cells displayed resistance to reovirus-induced oncolysis and bystander cytokine-killing but remained susceptible to killing by reovirus-activated NK cells and MM-specific cytotoxic T lymphocytes.ConclusionThese data highlight the importance of reovirus-induced immunotherapy for targeting MM cells within the BM niche and suggest that combination with agents which boost antitumor immune responses should be a priority.

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