MEK/ERK pathway mediates cytoprotection of salvianolic acid B against oxidative stress-induced apoptosis in rat bone marrow stem cells.
ABSTRACT To improve the survival and/or differentiation of grafted BMSCs (bone marrow stem cells) represents one of the challenges for the promising cell-based therapy. Considerable reports have implicated Sal B (salvianolic acid B), a potent aqueous extract of Salvia miltiorrhiza, in enhancing the survival of cells under various conditions. In this study, we investigated the effect of Sal B on H₂O₂-induced apoptosis in rat BMSCs, focusing on the survival signalling pathways. Results indicated that the MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] inhibitor (PD98059) and 10 μM Sal B remarkably prevented BMSCs from H₂O₂-induced apoptosis through attenuating caspase-3 activation, which is accompanied by the significant up-regulation of Bcl-2. In addition, the ROS (reactive oxygen species) accumulation was also reduced after Sal B treatment. Furthermore, Sal B inhibited the ERK1/2 phosphorylations stimulated by H₂O₂. Taken together, our results showed that H₂O₂-induced apoptosis in BMSCs via the ROS/MEK/ERK1/2 pathway and Sal B may exert its cytoprotection through mediating the pathway.
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ABSTRACT: Bone marrow contains a population of stem-like cells that can differentiate into neurons or glia. Stromal cells from green fluorescent protein (GFP)-expressing mice were isolated by initial separation on a density gradient and then cultured as adherent cells on plastic that proliferated in culture to confluency with a typical flattened elongative morphology. The large majority of the isolated stromal cells were GFP expressing and immunopositive for collagen type I, fibronectin, and CD44. Transplantation of these cells by direct microinjection into the demyelinated spinal cord of the immunosuppressed rat resulted in remyelination. The remyelinated axons showed characteristics of both central and peripheral myelination as observed by electron microscopy; conduction velocity of the axons was improved. GFP-positive cells and myelin profiles were observed in the remyelinated spinal cord region, indicating that the donor-isolated stromal cells were responsible for the formation of the new myelin. The GFP-positive cells were colocalized with myelin basic protein-positive and P0-positive cellular elements. These findings indicate that cells contained within the stromal cell fraction of the mononuclear cell layer of bone marrow can form functional myelin during transplantation into demyelinated spinal cord.Journal of Neuroscience 09/2002; 22(15):6623-30. · 6.91 Impact Factor
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ABSTRACT: Mesenchymal stem cells (MSCs) represent a promising source of material for autologous cell transplantation therapies, in particular, their potential use for the treatment of damaged nervous tissue. Much of the work in this area has focused on the transplantation of MSCs into animal models of neurological disorders, including stroke and spinal cord injury. Although numerous studies have reported significant functional improvements in these systems, the exact mechanism(s) by which MSCs elicit recovery remains largely undefined. While it has been proposed that 'trans'-differentiation and/or cell fusion events underly MSC-mediated neural repair, there is considerable doubt that the low frequency of these phenomena is sufficient to account for the observed levels of recovery. Furthermore, in vitro studies call into question the ability of MSCs to produce authentic neural derivatives. In this review we focus on recent evidence indicating that transplanted MSCs promote endogenous repair of neurologically damaged areas via the release of soluble trophic factors and cytokines. Through the modern analysis of MSC-conditioned media it is becoming possible to gain new insight into the release and interplay of these soluble factors and their neurogenic effects. Ultimately this understanding may lead to the rational design of new therapies for the treatment of neurological and neurodegenerative disorders.Current Stem Cell Research & Therapy 02/2008; 3(1):43-52. · 2.96 Impact Factor
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ABSTRACT: Transplantation of neonatal cardiomyocytes is a novel approach for the treatment of heart failure and myocardial infarction, but quantitative information on long-term cell survival and development is limited. Male donor cardiomyocytes were isolated from neonatal Fischer 344 rats (1-2 days), purified, and injected into the left ventricular wall of female syngeneic adult rats. One hour to 12 weeks later, genomic DNA was isolated from recipient hearts. The amount of male DNA per sample was determined by quantitative real-time TaqMan PCR of the male-specific Sry gene. Transplanted cell survival was 57 +/- 9% at 0-1 h, 24 +/- 6% at 24 h, 28 +/- 11% at 7 days, 27 +/- 3% at 14 days, 23 +/- 8% at 4 weeks and 15 +/- 3% at 12 weeks. The caspase inhibitor AcYVADcmk failed to improve transplanted cell survival at 24 h, suggesting that apoptosis did not play a major role in cell loss. Histology revealed that transplanted cells became more elongated over time, developed cross-striations, and that their nuclei increased in size. However, at 12 weeks, transplanted cells and their nuclei were still smaller than those of host myocardium. We established a quantitative survival profile for neonatal cardiomyocytes transplanted into normal adult myocardium. There was significant loss of cells within 24 h, but 15% of transplanted cells survived 12 weeks. Those cells that did survive underwent differentiation and developed visible sarcomeres, suggesting a potential contribution toward ventricular function.Journal of Molecular and Cellular Cardiology 03/2002; 34(2):107-16. · 5.15 Impact Factor