RESUMO
BACKGROUND: Stem cells have shown promising potential to treat burn wounds. Erythropoietin was capable of promoting in vitro transdifferentiation of mesenchymal stem cells (MSCs). The aim of the study was to investigate possible role of erythropoietin-pretreated mesenchymal stem cells (EPOa/MSCs) in burn wounds healing and to evaluate its in vivo differentiation into keratinocytes. MATERIALS AND METHODS: Forty rats were utilised in this study divided into four groups (n = 10 for each). Control group (I), burn group (II), burn + MSCs, group (III), burn + EPOa/MSCs. 1 × 106 cells were injected locally for each 1 cm² of burn areas. Burn areas were followed-up morphologically. After 21 days of the experiment, the rats were euthanised, skin specimens were assessed biochemically, histologically and immunohistochemically. RESULTS: EPOa/MSCs enhanced significantly (p < 0.05) burn wound vimentin gene expression and level of interleukin (IL)-10 while decreased IL-1 and COX2 as compared to the burn group. Histologically, EPOa/MSCs improved epithelialisation despite stem cells' differentiation into keratinocytes was rarely detected by PKH26 red fluorescence. EPOa/MSCs promoted angiogenesis as detected by significant increase in VEGF and PDGF immunoexpression as compared to burn group. CONCLUSIONS: EPOa/MSCs may improve burn wound healing, probably through anti-inflammatory, immunomodulatory and angiogenic action. However, in vivo transdifferentiation into keratinocytes was rarely detected.
Assuntos
Queimaduras/terapia , Transdiferenciação Celular , Eritropoetina/uso terapêutico , Queratinócitos/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Cicatrização , Animais , Biomarcadores/metabolismo , Proliferação de Células/genética , Transdiferenciação Celular/efeitos dos fármacos , Eritropoetina/farmacologia , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Compostos Orgânicos/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Ratos , Pele , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vimentina/genética , Vimentina/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
Although the risks of smoking are well known, the effects of exposure to nicotine on endocrine functions remain unclear. We investigated the deleterious effects of nicotine on the adrenal gland and the mechanisms of these changes in rats. The role of melatonin in ameliorating pathological changes also was investigated. We used 24 rats divided into four groups of six: group 1, control; group 2, nicotine treated; group 3, nicotine and melatonin treated; group 4, melatonin treated. We used histology; immunohistochemistry of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and tyrosine hydroxylase (TH); measured oxidative and antioxidative markers, malondialdehyde (MDA) and glutathione (GSH); and performed real-time PCR for NF-κB 65, IL1-B and IL6. We also performed histomorphometric analysis. Indentation and lamellar separation of the adrenal capsule, vacuolated degenerated cells and lymphocytic infiltration were observed in group 2. Vacuolated cells and cells with pyknotic nuclei also were detected in the zona reticularis and medulla of the same group. We observed improved shape and cellular lining of the gland in groups 3 and 4. Widespread expression of iNOS, VEGF and TH, increased area percent collagen, decreased GSH (56%) and increased MDA, NF-κB, IL1-B and IL-6 were observed in group 2. All parameters were ameliorated in groups 3 and 4. The effects of nicotine on the adrenal gland can be attributed to oxidative and inflammatory stress; melatonin ameliorates these effects.
