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Background Periodontal disease is a degenerative illness that leads to resorption of the alveolar bone. Mesenchymal stromal cells (MSC) represent a novel tool for the production of biologic constructs for the treatment of degenerative bone diseases. The preparation of MSC differentiated into osteogenic lineage for clinical use requires the fulfillment of strict good manufacturing practice (GMP) procedures. Methods MSC were isolated from BM samples and then cultured under GMP conditions. MSC were characterized phenotypically and for their differentiative potential. Cells were seeded onto collagen scaffolds (Gingistat) and induced to differentiate into osteogenic lineages using clinical grade drugs compared with standard osteogenic supplements. Alizarin Red S stain was used to test the deposition of the mineral matrix. Standard microbiologic analysis was performed to verify the product sterility. Results The resulting MSC were negative for CD33, CD34 and HLA-DR but showed high expression of CD90, CD105 and HLA-ABC (average expressions of 94.3%, 75.8% and 94.2%, respectively). Chondrogenic, osteogenic and adipogenic differentiation potential was demonstrated. The MSC retained their ability to differentiate into osteogenic lineage when seeded onto collagen scaffolds after exposure to a clinical grade medium. Cell numbers and cell viability were adequate for clinical use, and microbiologic assays demonstrated the absence of any contamination. Discussion In the specific context of a degenerative bone disease with limited involvement of skeletal tissue, the combined use of MSC, exposed to an osteogenic clinical grade medium, and biomimetic biodegradable scaffolds offers the possibility of producing adequate numbers of biologic tissue-engineered cell-based constructs for use in clinical trials. [ABSTRACT FROM AUTHOR]

We have demonstrated in the SH-SY5Y human neuroblastoma cell line that the antineoplastic drug paclitaxel induces apoptosis associated with the phosphorylation of c-raf and Bcl-2, thus causing Bcl-2 inactivation. In addition, we have observed the cleavage of caspase 7 and PARP, and the involvement of JNK/SAPK cascade. In this study, we investigated the possible anti-apoptotic effect of resveratrol on paclitaxel-induced apoptosis. Resveratrol is a natural antioxidant occurring in grapes and wine that as been shown to have anticancer and anti-inflammatory effects. Studies on the effect(s) of resveratrol on nervous cells are very few and limited to testing its ability in preventing oxidative stress in rat pheocromocytoma PC12 cells. However, the biological and pharmacological properties of resveratrol suggest that this natural compound might act on neuronal cells with a mode of action that is different from the antioxidant ones. To confirm this hypothesis, we studied the possible antagonist effect(s) of resveratrol on paclitaxel-induced apoptosis pathways. Our results indicate that the simultaneous treatment of 50M resveratrol and 1M paclitaxel induces a significant reduction of the percentage of apoptotic cells in comparison with 1M paclitaxel alone. Furthermore, we have demonstrated that resveratrol treatment determines a significant reduction of the phosphorylation of c-raf and Bcl-2 and a partial reduction of cleavage of caspase 7 and PARP. Finally, we observed an evident reduction of activation of JNK/SAPK in the presence of resveratrol. On the contrary, resveratrol does not affect the tubulin polymerization induced by paclitaxel. In conclusion, our results suggest that resveratrol is able to partially antagonize a nonoxidative stress apoptotic stimulus by influencing the typical signal pathways involved in apoptosis. [ABSTRACT FROM AUTHOR]