scholarly journals Influence of Egr-1 in Cardiac Tissue-Derived Mesenchymal Stem Cells in Response to Glucose Variations

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Daniela Bastianelli ◽  
Camilla Siciliano ◽  
Rosa Puca ◽  
Andrea Coccia ◽  
Colin Murdoch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Target Genes ◽  
Cardiac Tissue ◽  
Early Response ◽  
Induced Response ◽  
Protein Levels ◽  
Short Period ◽  
Phenotype Analysis

Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our aim was to investigate how short-term changes inin vitroglucose concentrations affect multipotent cardiac tissue-derived MSCs (cMSCs) in a mouse model of Egr-1 KO (Egr-1−/−). Results showed that loss of Egr-1 does not significantly influence cMSC proliferation. In contrast, responses to glucose variations were observed in wt but not in Egr-1−/−cMSCs by clonogenic assay. Phenotype analysis by RT-PCR showed that cMSCs Egr-1−/−lost the ability to regulate the glucose transporters GLUT-1 and GLUT-4 and, as expected, the Egr-1 target genes VEGF, TGFβ-1, and p300. Acetylated protein levels of H3 histone were impaired in Egr-1−/−compared to wt cMSCs. We propose that Egr-1 acts as immediate glucose biological sensor in cMSCs after a short period of stimuli, likely inducing epigenetic modifications.

scholarly journals Isolation, Characterization, and Agent-Based Modeling of Mesenchymal Stem Cells in a Bio-construct for Myocardial Regeneration Scaffold Design

Data ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 71 ◽  
Author(s):  
Diana Victoria Ramírez López ◽  
María Isabel Melo Escobar ◽  
Carlos A. Peña-Reyes ◽  
Álvaro J. Rojas Arciniegas ◽  
Paola Andrea Neuta Arciniegas
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
In Silico ◽  
Cardiac Tissue ◽  
Cellular Level ◽  
Cell Behavior ◽  
Agent Based Model ◽  
Agent Based ◽  
And Migration

Regenerative medicine involves methods to control and modify normal tissue repair processes. Polymer and cell constructs are under research to create tissue that replaces the affected area in cardiac tissue after myocardial infarction (MI). The aim of the present study is to evaluate the behavior of differentiated and undifferentiated mesenchymal stem cells (MSCs) in vitro and in silico and to compare the results that both offer when it comes to the design process of biodevices for the treatment of infarcted myocardium in biomodels. To assess in vitro behavior, MSCs are isolated from rat bone marrow and seeded undifferentiated and differentiated in multiple scaffolds of a gelled biomaterial. Subsequently, cell behavior is evaluated by trypan blue and fluorescence microscopy, which showed that the cells presented high viability and low cell migration in the biomaterial. An agent-based model intended to reproduce as closely as possible the behavior of individual MSCs by simulating cellular-level processes was developed, where the in vitro results are used to identify parameters in the agent-based model that is developed, and which simulates cellular-level processes: Apoptosis, differentiation, proliferation, and migration. Thanks to the results obtained, suggestions for good results in the design and fabrication of the proposed scaffolds and how an agent-based model can be helpful for testing hypothesis are presented in the discussion. It is concluded that assessment of cell behavior through the observation of viability, proliferation, migration, inflammation reduction, and spatial composition in vitro and in silico, represents an appropriate strategy for scaffold engineering.

Mesenchymal stem cells derived from Wharton's jelly: Comparative phenotype analysis between tissue and in vitro expansion

2012 ◽  
Vol 22 (4) ◽  
pp. 243-254 ◽  
Author(s):  
Talar Margossian ◽  
Loic Reppel ◽  
Nehman Makdissy ◽  
Jean-François Stoltz ◽  
Danièle Bensoussan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Wharton's Jelly ◽  
Phenotype Analysis ◽  
In Vitro Expansion

scholarly journals Evaluation of Priming Efficiency of Forskolin in Tissue-Specific Human Mesenchymal Stem Cells into Dopaminergic Neurons: An In Vitro Comparative Study

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2058
Author(s):  
Manisha Singh ◽  
Pardeep Kumar Vaishnav ◽  
Amit Kumar Dinda ◽  
Sujata Mohanty
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Calcium Ion ◽  
Dopaminergic Neurons ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells ◽  
Generate Functional ◽  
Efficient Manner ◽  
Protein Levels

Background: Human mesenchymal stem cells (hMSC) can be derived from various tissue sources and differentiated into dopaminergic (DAergic) neurons using various types of inducers. There are several strategies that have been reported to generate functional dopaminergic neuronal cells from hMSCs in the most efficient manner possible. However, this area is still under extensive research. In this study, we aim to compare hMSCs derived from bone marrow (BM), adipose tissue (AD) and dental pulp (DP) to generate functional dopaminergic neurons, using FGF2 and forskolin. Post-differentiation, multiple factors were used to characterize the cells at morphological, morphometric, ultra-structural, mRNA and protein levels for various markers (Nestin, NF, MAP2, Tuj1, TH, DAT, PitX3, Ngn2, Kv4.2, SCN5A). Cells’ functionality was studied by calcium ion imaging, along with the amount of dopamine secreted by the cells in the culture medium. Results: Data analysis revealed that forskolin has comparable effect on BM- and AD-derived MSC (28.43% and 29.46% DAergic neurons, respectively), whereas DP-MSC (42.78 ± 1.248% DAergic neurons) show better outcome in terms of efficient generation of DAergic neuronal cells, expression of neuronal associated markers, dopamine release and calcium ion efflux. Ultra-structural studies by SEM and TEM also revealed a substantial change in both cellular morphology and composition of cellular organelles. It was observed that AD-MSCs showed the best neuronal features, at morphological, gene, and protein levels upon induction with the above-mentioned induction cocktail. Conclusion: It may be concluded that a combination of FGF2 and forskolin yields functionally active dopaminergic neuronal cells in vitro, with highest percentage of the same from AD-MSCs, as compared to that in BM-MSCs and DP-MSCs. The outcomes and comparative evaluation provide a substantial platform for further studies on molecular pathways involved in the process of DAergic neurogenesis in individual cases.

scholarly journals Let-7c regulates proliferation and osteodifferentiation of human adipose-derived mesenchymal stem cells under oxidative stress by targeting SCD-1

2019 ◽  
Vol 316 (1) ◽  
pp. C57-C69 ◽  
Author(s):  
Zihui Zhou ◽  
Yuanshan Lu ◽  
Yao Wang ◽  
Lin Du ◽  
Yunpeng Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Postmenopausal Osteoporosis ◽  
Luciferase Reporter ◽  
Matrix Mineralization ◽  
Protein Levels ◽  
Micro Rnas

Osteoporosis is a progressive bone disease characterized by decreased bone mass and density, which usually parallels a reduced antioxidative capacity and increased reactive oxygen species formation. Adipose-derived mesenchymal stem cells (ADMSCs), a population of self-renewing multipotent cells, are a well-recognized source of potential bone precursors with significant clinical potential for tissue regeneration. We previously showed that overexpressing stearoyl-CoA desaturase 1 (SCD-1) promotes osteogenic differentiation of mesenchymal stem cells. Micro-RNAs (miRNAs) are noncoding RNAs recently recognized to play key roles in many developmental processes, and miRNA let-7c is downregulated during osteoinduction. We found that let-7c was upregulated in the serum of patients with postmenopausal osteoporosis compared with healthy controls. Levels of let-7c during osteogenic differentiation of ADMSCs were examined under oxidative stress in vitro and found to be upregulated. Overexpression of let-7c inhibited osteogenic differentiation, whereas inhibition of let-7c function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase activity, and matrix mineralization. The luciferase reporter assay was used to validate SCD-1 as a target of let-7c. Further experiments showed that silencing of SCD-1 significantly attenuated the effect of let-7c inhibitor on osteoblast markers, providing strong evidence that let-7c modulates osteogenic differentiation by targeting SCD-1. Inhibition of let-7c promoted the translocation of β-catenin into nuclei, thus activating Wnt/β-catenin signaling. Collectively, these data suggest that let-7c is induced under oxidative stress conditions and in osteoporosis, reducing SCD-1 protein levels, switching off Wnt/β-catenin signaling, and inhibiting osteogenic differentiation. Thus, let-7c may be a potential therapeutic target in the treatment of osteoporosis and especially postmenopausal osteoporosis.

scholarly journals Surface topography is a context-dependent activator of TGF-β signaling in mesenchymal stem cells

2020 ◽  
Author(s):  
Steven Vermeulen ◽  
Nadia Roumans ◽  
Floris Honig ◽  
Aurélie Carlier ◽  
Dennie G.A.J. Hebels ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Target Genes ◽  
Receptor Gene ◽  
Early Response ◽  
Gene Encoding ◽  
Actin Reorganization ◽  
Smad Phosphorylation ◽  
Synergistic Induction ◽  
Serum Response

AbstractWe previously found that surface topographies induce the expression of the Scxa gene, encoding Scleraxis in tenocytes. Because Scxa is a TGF-β responsive gene, we investigated the link between mechanotransduction and TGF-β signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-β2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-β target genes SCXA, a-SMA, and SOX9. Pharmacological perturbations revealed that Rho/ROCK/SRF signaling is required for this synergistic response. We further found an activation of the early response genes SRF and EGR1 during the early adaptation phase on micro-topographies, which coincided with higher expression of the TGF-β type-II receptor gene. Of interest, PKC activators Prostratin and Ingenol-3, known for inducing actin reorganization and activation of serum response elements, were able to mimic the topography-induced TGF-β response. These findings provide novel insights into the convergence of mechanobiology and TGF-β signaling, which can lead to improved culture protocols and therapeutic applications.

Mesenchymal stem cells pretreated with melatonin ameliorate kidney functions in a rat model of diabetic nephropathy

2018 ◽  
Vol 96 (5) ◽  
pp. 564-571 ◽  
Author(s):  
Laila Ahmed Rashed ◽  
Samah Elattar ◽  
Nashwa Eltablawy ◽  
Hend Ashour ◽  
Lamiaa Mohamed Mahmoud ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Nephropathy ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Kidney Tissue ◽  
Beclin 1 ◽  
Protein Levels ◽  
Kidney Functions

The aim of this study was to investigate the effect of a regenerative therapy comprising mesenchymal stem cells (MSCs) pretreated with melatonin (MT) as a new therapy for underlying diabetic nephropathy (DN) pathogenesis in a rat model, and its possible effect on autophagy protein Beclin-1. Forty adult male albino Wistar rats were distributed among 4 groups: (i) control, (ii) DN, (iii) MSC-treated, and (iv) treated with MSCs that were pre-incubated in-vitro with MT (5 μmol·L–1 for 24 h; MSCs + MT). MSCs treatment significantly improved the renal functions and ameliorated the measured underlying DN pathogenesis and elevation of Beclin-1 protein levels compared with the DN group. In-vitro pretreatment of MSCs with MT enhanced proliferation and efficiency, and thus improved the kidney functions by increasing superoxide dismutase (SOD-1) and Beclin-1, and decreasing transforming growth factor (TGF-β) markers in the kidney tissue, compared with the MSC group (P < 0.05). In conclusion: MSCs represent a promising target in DN management, and their effect can be intensified by pretreatment with MT. The elevated levels of Beclin-1 could be a mediator.

Apigenin promotes osteogenic differentiation of mesenchymal stem cells and accelerates bone fracture healing via activating Wnt/β-catenin signaling

2021 ◽  
Author(s):  
Fei-fei Pan ◽  
Jiang Shao ◽  
Chuan-jian Shi ◽  
Zhi-peng Li ◽  
Wei-ming Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fracture Healing ◽  
Osteogenic Differentiation ◽  
Bone Fracture ◽  
Fruits And Vegetables ◽  
Target Genes ◽  
Fracture Repair

Apigenin (API), a natural plant flavone, is abundantly found in common fruits and vegetables. As a bioactive flavonoid, API exhibits several activities including anti-proliferation and anti-inflammation. A recent study showed that API could retard osteoporosis progress, indicating its role in the skeletal system. However, the detailed function and mechanism remain obscure. In the present study, API was found to promote osteogenic differentiation of mesenchymal stem cells (MSCs). And further investigation showed that API could enhance the expression of the critical transcription factor β-catenin and several downstream target genes of Wnt signaling, thus activated Wnt/β-catenin signaling. Using a rat femoral fracture model, API was found to improve new bone formation and accelerate fracture healing in vivo. In conclusion, our data demonstrated that API could promote osteogenesis in vitro and facilitate the fracture healing in vivo via activating Wnt/β-catenin signaling, indicating that API may be a promising therapeutic candidate for bone fracture repair.

scholarly journals Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Chang Liu ◽  
Huayong Zhang ◽  
Xiaojun Tang ◽  
Ruihai Feng ◽  
Genhong Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Joint Damage ◽  
Marker Genes ◽  
Micro Ct ◽  
Bone Morphology ◽  
Protein Levels ◽  
Morphology Parameters

Objective. To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods. CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the bone morphology parameters. Osteogenic differentiation of treated CIA mice was determined. Bone marrow mesenchymal stem cells (BM-MSCs) from CIA mice were treated with TNF-α in vitro to explore their effects on osteogenesis. Results. The arthritis score was significantly reduced in the UC-MSC transplantation and anti-TNF-α-treated CIA groups, compared with control mice (P<0.001). Micro-CT showed that CIA mice developed osteoporosis at 12 weeks after immunization. The bone morphology parameters were partially improved in UC-MSC-treated CIA mice. Impaired osteogenic differentiation functions were indicated by decreased ALP activity (P<0.001) and reduced mRNA and protein levels of osteogenic marker genes (P<0.05) in CIA mice compared with DBA/1 mice. UC-MSC treatment significantly upregulated the impaired osteogenic differentiation ability in CIA mice. Meanwhile, the serum TNF-α level was decreased significantly in the UC-MSC group. The osteogenesis was reduced with the addition of TNF-α in vitro. Conclusion. This study demonstrated that UC-MSC transplantation not only significantly improved the joint damage but also played a beneficial role in osteoporosis in CIA mice. Mechanistically, the improved osteogenic differentiation of CIA under UC-MSC treatment may be achieved by inhibition of TNF-α.

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