Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Cell Death Dis ; 9(1): 1, 2018 01 03.
Article in English | MEDLINE | ID: mdl-29298988

ABSTRACT

Cell engraftment, survival and integration during transplantation procedures represent the crux of cell-based therapies. Thus, there have been many studies focused on improving cell viability upon implantation. We used severe oxidative stress to select for a mouse mesoangioblast subpopulation in vitro and found that this subpopulation retained self-renewal and myogenic differentiation capacities while notably enhancing cell survival, proliferation and migration relative to unselected cells. Additionally, this subpopulation of cells presented different resistance and recovery properties upon oxidative stress treatment, demonstrating select advantages over parental mesoangioblasts in our experimental analysis. Specifically, the cells were resistant to oxidative environments, demonstrating survival, continuous self-renewal and improved migration capability. The primary outcome of the selected cells was determined in in vivo experiments in which immunocompromised dystrophic mice were injected intramuscularly in the tibialis anterior with selected or non-selected mesoangioblasts. Resistant mesoangioblasts exhibited markedly enhanced survival and integration into the host skeletal muscle, accounting for a more than 70% increase in engraftment compared with that of the unselected mesoangioblast cell population and leading to remarkable muscle recovery. Thus, the positive effects of sorting on mesoangioblast cell behaviour in vitro and in vivo suggest that a selection step involving oxidative stress preconditioning may provide a novel methodology to select for resistant cells for use in regenerative tissue applications to prevent high mortality rates upon transplantation.


Subject(s)
Hydrogen Peroxide/pharmacology , Oxidative Stress/drug effects , Animals , Cell Cycle Checkpoints/drug effects , Cell Differentiation , Cell Line , Cell Movement/drug effects , Cell Survival/drug effects , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Mice , Mice, SCID , Muscle, Skeletal/cytology , Muscular Dystrophy, Animal/therapy , Protein Isoforms/metabolism , Reactive Oxygen Species/metabolism , Sarcoglycans/deficiency , Sarcoglycans/genetics , Stem Cell Transplantation , Stem Cells/cytology , Stem Cells/drug effects , Stem Cells/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
2.
J Cell Physiol ; 232(7): 1845-1861, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27925208

ABSTRACT

Mouse mesoangioblasts are vessel-associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. Therefore, they represent a promising tool in the regeneration of injured tissues. Several studies have demonstrated that homing of mesoangioblasts into blood and injured tissues are mainly controlled by cytokines/chemokines and other inflammatory factors. However, little is known about the molecular mechanisms regulating their ability to traverse the extracellular matrix (ECM). Here, we demonstrate that membrane vesicles released by mesoangioblasts contain Hsp70, and that the released Hsp70 is able to interact by an autocrine mechanism with Toll-like receptor 4 (TLR4) and CD91 to stimulate migration. We further demonstrate that Hsp70 has a positive role in regulating matrix metalloproteinase 2 (MMP2) and MMP9 expression and that MMP2 has a more pronounced effect on cell migration, as compared to MMP9. In addition, the analysis of the intracellular pathways implicated in Hsp70 regulated signal transduction showed the involvement of both PI3K/AKT and NF-κB. Taken together, our findings present a paradigm shift in our understanding of the molecular mechanisms that regulate mesoangioblast stem cells ability to traverse the extracellular matrix (ECM). J. Cell. Physiol. 232: 1845-1861, 2017. © 2016 Wiley Periodicals, Inc.


Subject(s)
Autocrine Communication , Cell Movement , Extracellular Space/metabolism , HSP70 Heat-Shock Proteins/metabolism , Signal Transduction , Animals , Endothelial Cells , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Membrane Microdomains/metabolism , Mice , Models, Biological , NF-KappaB Inhibitor alpha , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protein Binding , Proto-Oncogene Proteins c-akt/metabolism , Toll-Like Receptor 4/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...