scholarly journals TRAIL-transduced multipotent mesenchymal stromal cells (TRAIL-MSC) overcome TRAIL resistance in selected CRC cell lines in vitro and in vivo

2010 ◽  
Vol 18 (4) ◽  
pp. 229-239 ◽  
Author(s):  
L P Mueller ◽  
J Luetzkendorf ◽  
M Widder ◽  
K Nerger ◽  
H Caysa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Trail Resistance

scholarly journals Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Per Anderson ◽  
Elena Gonzalez-Rey ◽  
Francisco O’Valle ◽  
Francisco Martin ◽  
F. Javier Oliver ◽  
...  
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Function ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Brain Inflammation ◽  
Inos Inhibitor ◽  
Cox 1

Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS-) induced maturation of dendritic cells (DCs) in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG) E2 in this process. In vivo, early administration of murine and human ASCs (hASCs) ameliorated myelin oligodendrocyte protein- (MOG35-55-) induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+CD40high and CD11c+TNF-α+) DCs in draining lymph nodes (DLNs). In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.

scholarly journals Gremlin1 Delivered by Mesenchymal Stromal Cells Promoted Epithelial-Mesenchymal Transition in Human Esophageal Squamous Cell Carcinoma

2018 ◽  
Vol 47 (5) ◽  
pp. 1785-1799 ◽  
Author(s):  
Dongxi Hong ◽  
Te Liu ◽  
Weijun Huang ◽  
Yan Liao ◽  
Lin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

Backgroud/Aims: Mesenchymal stromal cells (MSCs) are a major component of the tumor microenvironment (TME). Several studies focusing on tumor-derived MSCs have demonstrated that they exhibit a strong ability to promote the tumor epithelial-mesenchymal transition (EMT). However, the factors mediating these effects are poorly understood. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry assays were used to detect the expression of Gremlin1 (GREM1) in human esophageal squamous cell carcinoma (ESCC) tissues. ShRNA silencing, flow cytometry, cell counting kit (CCK8) assay, invasion assay, western blot were used to detect the effect of GREM1 in ECa109, TE-1 cell lines and xenograft tumor models. Results: In the current study, we found that the GREM1 was overexpressed in human ESCC tissues. The conditioned medium from mesenchymal stromal cells (MSCs-CM) enhanced the malignancy of xenograft esophageal tumors in vivo, as well as the cell proliferation, viability and invasion of the esophageal carcinoma cell lines ECa109 and TE-1 in vitro. Furthermore, the shRNA silencing of GREM1 in MSCs (shGREM1-MSCs) reversed the increased malignancy of the esophageal tumor in vivo, while the conditioned medium from shGREM1-MSCs (shGREM1-MSCs-CM) affected the cell cycle and cell invasion in vitro. These processes were accompanied by the EMT in the ECa109 and TE-1 cell lines with an alteration in the expression levels of mesenchymal and epithelial markers. Furthermore, the TGF-β/BMP (transforming growth factor-beta/bone morphogenetic protein) signaling pathway participated in the shGREM1-MSCs-CM-induced anti-tumor effect on enhanced esophageal malignancy induced by MSCs-CM treatment. Conclusions: Taken together, our study suggested that GREM1 delivered by MSCs promoted EMT in ESCC in vitro and in vivo, which is partly through TGF-β/BMP signaling pathway. The results provide experimental evidence to a potential therapeutic target in the treatment of esophageal cancer.

scholarly journals Allogeneic Bone Marrow Multipotent Mesenchymal Stromal Cells and Polytrauma Repair: The Role of Fractionated on the Basis of Molecular Mass Red Beetroot Juice in the Prevention of Transplanted Cells Side Effects in Rats

2013 ◽  
Vol 67 (1) ◽  
pp. 52-60
Author(s):  
Dmitrijs Babarikins ◽  
Guntra Krūmiņa ◽  
Irina Paegle ◽  
Diāna Amerika ◽  
Zaiga Krūmiņa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Total Phenolic ◽  
Allogeneic Bone ◽  
Beetroot Juice

Red beetroot (Beta vulgaris) juice (RBJ) is used as a traditional medicine for treatment of anemia. It has been shown that beetroot juice decreases blood pressure, provides a protective effect on blood vessels and has antioxidant and anticancerogenic properties. In the case of polytrauma it might have beneficial effects because of its antioxidant and anti-inflammatory properties as well as antimicrobial activity. It is also well-known that RBR juice can induce undesirable side effects, e.g. flatulent stomach, nausea and other unpleasant reactions. Therefore, it seems prospective to develop red beetroot juice based on its natural compound composition free of undesirable side effects, which could then be used in combination with bone marrow multipotent mesenchymal stromal cells (BM MMSC) transplantation in the case of polytrauma. The aim of the study was to evaluate the therapeutic effect of allogeneic BM MMSC transplantation in rats with experimental polytrauma and to analyse red beetroot fractions separated on the basis of molecular weight in regard to their ingestion impact on cell transplantation efficacy. Red beet juice was fractionated by ultrafiltration (cut-off-point 20 kDa). Total phenolic compound concentration in the final product practically did not decrease. The product was tested in vitro and in vivo. Unlike native juice, fractionated RBJ in vitro suppressed BM MMSC adipogenic (60-71%, P < 0.05) and stimulated osteogenic differentiation (124%, P < 0.05). Experimental polytrauma in rats was modelled by causing three fractures and haemorrhagic shock. Animals were randomised in five groups: 1) normal control; 2) polytrauma; 3) polytrauma + i/v BM MMSC transplantation 36 h and 5 days after surgery; 4) polytrauma + fractionated RBJ administration per os 1ml/d, and 5) polytrauma + BM MMSCs + fractionated RBJ. Transplantation of allogeneic BM MMSCs in rats with experimental polytrauma stimulated bone fracture reparation, but caused plethora in viscera and dystrophic changes in lungs. Combination of BM MMSCs and fractionated RBJ resulted in better bone reparation and significant hematopoiesis stimulation.

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 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Sciatic Nerve Injury ◽  
Motor Deficits ◽  
3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

scholarly journals Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 403
Author(s):  
Girolamo Di Maio ◽  
Nicola Alessio ◽  
Ibrahim Halil Demirsoy ◽  
Gianfranco Peluso ◽  
Silverio Perrotta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
White Adipocyte ◽  
Drug Candidates ◽  
Fat Depots ◽  
Treatment Of Obesity ◽  
White Fat

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

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