Stem cells represent promising candidates for regenerative therapy of craniomaxillofacial bone defects, where common techniques, such as autogenous bone graft, allografts or others possess shortcomings and limitations in restoring the morphology and function in bone loss. The efficacy of regenerative therapy with mesenchymal stromal cells (MSC) depends on a combination of the interactions between transplanted MSCs and cellular and molecular components of the recipient, and any current pharmacotherapy in the recipient with effects on transplanted MSC and the bone microenvironment. In the present investigation, dental pulp stem cells (DPSC) were isolated from human impacted third molar teeth. DPSC were treated with ibuprofen in vitro at clinically relevant concentration and relative expression of selected genes were assessed. Our preliminary data suggest a significant effect of ibuprofen as indicated by upregulation of the relative expression levels of growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). While the effects of stem cell therapy in bone regeneration are being investigated in ongoing clinical trials, the effects of commonly used pharmacotherapy should be studied for its potential impact on the paracrine effects of stem cells and consequently bone regenerative processes.

• MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• exprese genu MeSH
• hepatocytární růstový faktor MeSH
• ibuprofen * terapeutické užití   MeSH
• kmenové buňky MeSH
• lebka patologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * MeSH
• nemoci kostí farmakoterapie   terapie   MeSH
• parakrinní signalizace MeSH
• polymerázová řetězová reakce MeSH
• regenerativní lékařství metody   MeSH
• techniky in vitro metody   MeSH
• vaskulární endoteliální růstový faktor A MeSH
• Check Tag
• lidé MeSH

Autologous stem cell therapy is the most promising alternative treatment in patients with chronic ischemic diseases, including ischemic heart disease and critical limb ischemia, which are characterized by poor prognosis related to serious impair of quality of life, high risk of cardiovascular events and mortality rates. However, one of the most serious shortcomings of stem cell transplantation are low survival after transplantation to the site of injury, as large number of stem cells are lost within 24 hours after delivery. Multiple studies suggest that combination of lipid-lowering drugs, statins, and stem cell transplantation might improve therapeutic efficacy in regenerative medicine. Statins are inhibitors of HMG-CoA reductase and belong to recommended therapy in all patients suffering from critical limb ischemia. Statins possess non-lipid effects which involve improvement of endothelial function, decrease of vascular inflammation and oxidative stress, anti-cancer and stem cell modulation capacities. These non-lipid effects are explained by inhibition of mevalonate synthesis via blocking isoprenoid intermediates synthesis, such as farnesylpyrophospate and geranylgeranylpyrophospate and result in modulation of the PI3K/Akt pathway. Moreover, statin-mediated microRNA regulation may contribute to the pleiotropic functions. MicroRNA interplay in gene regulatory network of IGF/Akt pathway may be of special significance for the treatment of critical limb ischemia. We assume further studies are needed for detailed analysis of statin interactions with microRNA at the molecular level and their link to PI3K/Akt and IGF/Akt pathway in stem cells, which are currently the most promising treatment strategy used in chronic ischemic diseases.

• MeSH
• atorvastatin * farmakologie   terapeutické užití   MeSH
• chronická kritická ischemie končetin * farmakoterapie   terapie   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• ischemie * farmakoterapie   terapie   MeSH
• končetiny * krevní zásobení   MeSH
• kvalita života MeSH
• lidé MeSH
• statiny * farmakologie   terapeutické užití   MeSH
• transplantace kmenových buněk * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.

• MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• fyziologická neovaskularizace MeSH
• ischemie metabolismus   terapie   MeSH
• kinázy asociované s rho metabolismus   MeSH
• lidé MeSH
• mezenchymální kmenové buňky metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH