Current Issue : October - December Volume : 2014 Issue Number : 4 Articles : 7 Articles
A growing body of evidence supports the argument that bone marrow-derived mesenchymal stem cells (MSCs) can differentiate\ninto cardiomyocyte-like cells in an appropriate cellular environment, but the differentiation rate is low. A cocktail method was\ndesigned: we investigated the role of 5-azacytidine (5-aza), salvianolic acid B (SalB), and cardiomyocyte lysis medium (CLM) in\ninducing MSCs to acquire the phenotypical characteristics of cardiomyocytes. The fourth-passage MSCs were treated with 5-aza,\nSalB, CLM, 5-aza+salB, 5-aza+CLM, SalB+CLM, and 5-aza+SalB+CLM for 2 weeks. Immunofluorescence results showed that cTnT\nexpression in the 5-aza+salB+CLM group was stronger than other groups. Real-time qPCR andWestern blotting analyses showed\nthat cTnT, alpha-cardiac actin, mef-2c, Cx43, and GSK-3beta expression increased while beta-catenin expression decreased. The\nsalB+5-aza+CLM group had the most evident effects. SalB combined with 5-aza and CLM improved cardiomyocyte differentiation\nfrom MSCs. In the MSCs differentiation process, theWnt/beta-catenin signaling pathway had been inhibited....
Enrichment of cancer stem cells (CSCs) is thought to be responsible for glioblastomamultiforme (GBM) recurrence after radiation\ntherapy. Simulation results fromour agent-based cellular automatamodel reveal that the enrichment of CSCs may result either from\nan increased symmetric self-renewal division rate of CSCs or a reprogramming of non-stem cancer cells (CCs) to a stem cell state.\nBased on plateau-to-peak ratio of the CSC fraction in the tumor following radiation, a downward trend from peak to subsequent\nplateau (i.e., a plateau-to-peak ratio exceeding 1.0) was found to be inconsistent with increased symmetric division alone and favors\ninstead a strong reprogramming component. The two contributions together are seen to be the product of a dynamic equilibrium\nbetween CSCs and CCs that is highly regulated by the kinetics of single cells, including the potential for CCs to reacquire a stem\ncell state and confer phenotypic plasticity to the population as a whole. We conclude that tumor malignancy can be gauged by a\ndegree of cancer cell plasticity....
Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition\nof the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms\ncontrolling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational\ncell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases,\nhave entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs) are nonhematopoietic cells\nwith multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow\nand other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce antiinflammatory\nmolecules which can modulate humoral and cellular immune responses. Considering their regenerative potential\nand immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune\ndiseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development,\nhomeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials....
Genetic modifications of bonemarrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to\nimprove their therapeutic potential and enable innovative strategies in tissue regeneration.However, most of the studies use cultured\nhMSCs, although these can lose their stem cell characteristics during expansion. Therefore, we aimed to develop a nonviral miR\ncarrier based on polyethylenimine (PEI) bound to magnetic nanoparticles (MNPs) for efficient miR delivery in freshly isolated\nhMSCs. MNP based transfection is preferable for genetic modifications in vivo due to improved selectivity, safety of delivery, and\nreduced side effects.Thus, in this study different miR/PEI and miR/PEI/MNP complex formulations were tested in vitro for uptake\nefficiency and cytotoxicity with respect to the influence of an external magnetic field. Afterwards, optimized magnetic complexes\nwere selected and compared to commercially available magnetic vectors (Magnetofectamine, CombiMag).We found that all tested\ntransfection reagents had high miR uptake rates (yielded over 60%) and no significant cytotoxic effects. Our work may become\ncrucial for virus-free introduction of therapeutic miRs as well as other nucleic acids in vivo.Moreover, in the field of targeted stem\ncell therapy nucleic acid delivery prior to transplantation may allowfor initial cell modulation in vitro....
Mesenchymal stromal cells (MSC) have great potential for cellular therapies as they can be directed to differentiate into certain\nlineages or to exert paracrine effects at sites of injury.The interactions between stromal cell-derived factor (SDF)-1 and its receptors\nCXCR4 and CXCR7 play pivotal roles in the migration of MSC to injured tissues. We evaluated whether a histone deacetylase\ninhibitor valproic acid (VPA) modulates the migration of cord blood (CB-) derived MSC towards SDF-1 and their proliferation and\ndifferentiation.We found that in MSC, VPA increased (i) the gene and total protein expression of CXCR4 and CXCR7 and primed\nmigration towards a low gradient of SDF-1, (ii) the gene expression of MMP-2 and secretion and activation of proMMP-2, (iii) the\nproliferation and gene expression of pluripotencymarkers SOX2 andOct-4, and exposure to lower concentrations of VPA (?5mM)\nhad no effect on their differentiation to osteocytes and chondrocytes.Thus, our study indicates that VPA enhances the migration\nof CB MSC towards SDF-1 by increasing the expression of CXCR4, CXCR7, and MMP-2. VPA at low concentrations may be used\nfor ex vivo treatment of MSC to increase their recruitment to sites of injury without compromising their ability to proliferate or\ndifferentiate....
The use of mesenchymal stem cells (MSCs) as clinical therapeutics is a relatively new avenue of study for treatment of a variety\nof diseases. The therapeutic impact of the MSCs is based upon their multiplicities of function and interaction with host tissues.\nMSCs can be anti-inflammatory, antifibrotic, antimicrobial, and regenerative, all which may improve outcomes in scenarios of\ndamaged tissues and inflammation. Although most studies focus on utilizing MSCs to direct clinical efficacy, it is the ability to\norchestrate host response in surrounding tissue that is especially unique and versatile. This orchestration of host response can be\napplied to a variety of clinical scenarios not only through cell-cell interactions but also through production of bioactive secreted\nfactors. These bioactive factors include small proteins, chemokines, cytokines, and other cellular regulators. These factors have the\ncapacity to induce angiogenesis or blood vessel development, be chemotactic, and induce cellular recruitment. MSCs also have the\ncapacity to differentiate with the implicated environment to regenerate tissue or accommodate host tissue in a cell specific manner.\nThe differentiation cannot only be done in vivo but also can be optimized in vitro prior to in vivo administration, potentiating the\nversatility of the MSCs and opening avenues for corrective therapy and cell delivery of genes. The differentiation process depends\non the environment with which the MSCs are put and results in active communication between the newly administered cells host\ntissue. Since these properties have been identified, there are a variety of clinical trials and studies being conducted on MSCs ability\nto treat human disease. This review outlines the potential use of MSCs, the types of tissue, and the innovative applications ofMSCs\nfor the treatment of diseases....
Introduction. Ingestion of corrosive substances may lead to stricture formation in esophagus as a late complication. Full thickness\ninjury seems to exterminate tissue stem cells of esophagus. Mesenchymal stem cells (MSCs) can differentiate into specific cell\nlineages and have the capacity of homing in sites of injury. Aim and Methods. We aimed to investigate the efficacy of MSC\ntransplantation, on prevention of esophageal damage and stricture formation after caustic esophagus injury in rats. 54 rats were\nallocated into four groups; 4 rats were sacrificed for MSC production. Group 1, untreated controls (????: 10). Group 2, membrane\nlabeled MSCs-treated rats (????: 20). Group 3, biodistribution of fluorodeoxyglucose labeledMSCs via positron emission tomography\n(PET) imaging (????: 10). Group 4, shamoperated (????: 10). Standard caustic esophageal burns were created and MSCs were transplanted\n24 hours after. All rats were sacrificed at the 21st days. Results. PET scan images revealed the homing behavior of MSCs to the injury\nsite.The histopathology damage score was not significantly different fromcontrols.However,we demonstrated Dil labeled epithelial\nand muscle cells which were originating from transplanted MSCs. Conclusion.MSC transplantation after caustic esophageal injury\nmay be a helpful treatment modality; however, probably repeated infusions are needed....
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