scholarly journals Modulation of Adult Mesenchymal Stem Cells Activity by Toll-Like Receptors: Implications on Therapeutic Potential

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Olga DelaRosa ◽  
Eleuterio Lombardo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Culture Conditions ◽  
Toll Like Receptors ◽  
Adult Mesenchymal Stem Cells ◽  
Special Relevance ◽  
Tlr Signalling

Mesenchymal stem cells (MSCs) are of special interest as therapeutic agents in the settings of both chronic inflammatory and autoimmune diseases. Toll-like receptors (TLR) ligands have been linked with the perpetuation of inflammation in a number of chronic inflammatory diseases due to the permanent exposure of the immune system to TLR-specific stimuli. Therefore, MSCs employed in therapy can be potentially exposed to TLR ligands, which may modulate MSC therapeutic potential in vivo. Recent results demonstrate that MSCs are activated by TLR ligands leading to modulation of the differentiation, migration, proliferation, survival, and immunosuppression capacities. However inconsistent results among authors have been reported suggesting that the source of MSCs, TLR stimuli employed or culture conditions play a role. Notably, activation by TLR ligands has not been reported to modulate the “immunoprivileged” phenotype of MSCs which is of special relevance regarding the use of allogeneic MSC-based therapies. In this review, we discuss the available data on the modulation of MSCs activity through TLR signalling.

scholarly journals The Modulatory Effects of Mesenchymal Stem Cells on Osteoclastogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Wessam E. Sharaf-Eldin ◽  
Nourhan Abu-Shahba ◽  
Marwa Mahmoud ◽  
Nagwa El-Badri
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Suppressive Effect ◽  
Osteoclast Formation ◽  
Inducing Factors ◽  
High Concentrations

The effect of mesenchymal stem cells (MSCs) on bone formation has been extensively demonstrated through severalin vitroandin vivostudies. However, few studies addressed the effect of MSCs on osteoclastogenesis and bone resorption. Under physiological conditions, MSCs support osteoclastogenesis through producing the main osteoclastogenic cytokines, RANKL and M-CSF. However, during inflammation, MSCs suppress osteoclast formation and activity, partly via secretion of the key anti-osteoclastogenic factor, osteoprotegerin (OPG).In vitro, co-culture of MSCs with osteoclasts in the presence of high concentrations of osteoclast-inducing factors might reflect thein vivoinflammatory pathology and prompt MSCs to exert an osteoclastogenic suppressive effect. MSCs thus seem to have a dual effect, by stimulating or inhibiting osteoclastogenesis, depending on the inflammatory milieu. This effect of MSCs on osteoclast formation seems to mirror the effect of MSCs on other immune cells, and may be exploited for the therapeutic potential of MSCs in bone loss associated inflammatory diseases.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

scholarly journals Adipose tissue-derived mesenchymal stem cells have better restorative capacity than bone marrow-derived cells in a cerebellar ataxic rat model

2020 ◽  
Author(s):  
Rasha Att ◽  
Angie Ameen ◽  
Horeya Korayem ◽  
Noha Abogresha ◽  
Yasser El-Wazir
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Motor Performance ◽  
Therapeutic Potential ◽  
Monosodium Glutamate ◽  
Control Group

IntroductionRegenerative treatment using stem cells represents a potentially effective therapy for cerebellar ataxia (CA). We compared the therapeutic potential of adipose tissue stem cells (ASCs) and bone marrow mesenchymal stem cells (BM-MSCs) in a rodent monosodium glutamate (MSG)-induced CA cell (BM-MSC) model.Material and methodsFemale Wistar rats (n = 40) were equally divided into a saline-treated control group and 3 MSG-induced CA groups randomly treated with either saline, or 1 × 106 ASCs or BM-MSCs. We assessed the following: 1) cerebellar motor functions in vivo (by Rotarod test, open-field test, and Quantitative gait analysis); 2) cerebellar histological architecture; and 3) cerebellar immunohistochemical examination of the Bax/Bcl-2 ratio as in indicator of apoptosis, and the levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) as neuroprotective factors.ResultsTreatment with either of the MSCs improved MSG-induced poor motor performance, restored the disrupted Purkinje cell layer, decreased neuronal apoptosis and enhanced cerebellar VEGF and IGF-1 levels observed in CA rats. Adipose tissue stem cells showed superiority over BM-MSCs in the improvement of some motor performance parameters and cerebellar VEGF and IGF-1 levels.ConclusionsIn conclusion, both stem cell types induced structural, physiological, and biochemical improvement, with ASCs being best for treatment of CA.

scholarly journals Toll-Like Receptor Expression of Mesenchymal Stem Cells Derived from Granulocyte Colony-Stimulating Factor Treated Bone Marrow Donors

Acta Medica ◽  
2020 ◽  
Vol 51 (4) ◽  
pp. 33-40
Author(s):  
Tekin Aksu ◽  
Neslihan Karakurt ◽  
İrem Akar ◽  
Yasin Köksal ◽  
Fatih M. Azık ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptors ◽  
Toll Like Receptor 2 ◽  
Stimulating Factor

Objective: The present study was planned to examine the expression of Toll-like receptors on human marrow-derived mesenchymal stem cells as a result of in-vivo exposure to granulocyte colony-stimulating factor with or without exposure of the cells to Toll-like receptors agonists. Materials and Methods: Toll-like receptor 2, 3, and 4 expressions of mesenchymal stem cells obtained from healthy human bone marrow donors exposed to in-vivo granulocyte colony-stimulating factor were analyzed, and granulocyte colony-stimulating factor untreated donors served as controls. Also, mesenchymal stem cells were stimulated in-vitro by Toll-like receptor agonists to observe the changes in the expression of the Toll-like receptors. Results: Mesenchymal stem cells obtained from both granulocyte colony-stimulating factor exposed or unexposed donors showed a low level of Toll-like receptor 2, 4 expressions by flow cytometry, whereas Toll-like receptor 3 expression was higher. Lipopolysaccharide was used as an agonist, but no significant difference was observed in the Toll-like receptor 2, 4 expressions, both in the granulocyte colony-stimulating factor exposed and unexposed groups. Stimulation of cells with Toll-like receptor 3 ligand was associated with a statistically significant decrease in Toll-like receptor 3 expressions, which was more profound in granulocyte colony-stimulating factor unexposed cells. Conclusion: We have shown that human bone marrow-derived culture-expanded mesenchymal stem cells express Toll-like receptor 3, whether in-vivo granulocyte colony-stimulating factor treated or untreated. Besides, the Toll-like receptor 3 agonist’s effect in lowering the expression levels was more significant in cells that were not exposed to granulocyte colony-stimulating factor. Additionally, detection of low expression of the pro-inflammatory Toll-like receptor 4 versus higher levels of Toll-like receptor 3 supports literature regarding the immunosuppressive characteristics of marrow-derived mesenchymal stem cells. Modulation of the expression of the Toll-like receptor of mesenchymal stem cells with granulocyte colony-stimulating factor or agonists may have implications in allogeneic mesenchymal stem cell therapies.

scholarly journals The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Li Chen ◽  
Jiexin Zhang ◽  
Lu Yang ◽  
Guoying Zhang ◽  
Yingjie Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Conditioned Medium ◽  
Therapeutic Potential ◽  
L02 Cells ◽  
Cells Cultured

Mesenchymal stem cells (MSCs) and hepatocytes are two attractive sources of cell-based therapies for acute liver failure (ALF). The cotransplantation of hepatocytes with MSCs can improve the therapeutic performance for the treatment of ALF. However, the therapeutic potential of conditioned medium (CM) derived from MSCs cocultured with hepatocytes (MSC-H-CM) remains unclear. The purpose of this study was to investigate the effects of MSC-H-CM on damaged hepatocytes in vitro and on D-galactosamine-induced ALF in vivo. D-Galactosamine-treated L02 cells cultured in MSC-H-CM exhibited higher of cell viability and total protein synthesis than L02 cells cultured in MSC-CM, CM derived from hepatocytes (H-CM), MSC-CM + H-CM, or with nonconditioned medium (NCM). Lactate dehydrogenase and aspartate aminotransferase levels were lower in the supernatant of damaged L02 cells cultured in MSC-H-CM than in that of L02 cells cultured in other types of CM. The lowest percentage of apoptotic cells was observed after the MSC-H-CM treatment. When CM was injected into the tail vein of rats with ALF, MSC-H-CM was the most successful at preventing the release of liver injury biomarkers and in promoting the recovery of liver structure. The greatest survival rate 7 days after the first treatment was observed in the MSC-H-CM-treated rats. Our results reveal that the delivery of MSC-H-CM could be a novel strategy for integrating the therapeutic potentials of hepatocytes and MSCs for the treatment of ALF.

scholarly journals In vivo priming of human mesenchymal stem cells with hepatocyte growth factor–engineered mesenchymal stem cells promotes therapeutic potential for cardiac repair

2020 ◽  
Vol 6 (13) ◽  
pp. eaay6994 ◽  
Author(s):  
Bong-Woo Park ◽  
Soo-Hyun Jung ◽  
Sanskrita Das ◽  
Soon Min Lee ◽  
Jae-Hyun Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Therapeutic Potential ◽  
Cardiac Repair ◽  
Vascular Regeneration ◽  
Cardiac Patch ◽  
Hepatocyte Growth

The clinical use of human bone marrow–derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)–induced hearts through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.

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