RESUMEN
Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.
Asunto(s)
Animales , Humanos , Masculino , Extremidades/irrigación sanguínea , /metabolismo , Expresión Génica , Isquemia/fisiopatología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Neovascularización Fisiológica/fisiología , Antígenos de Superficie/análisis , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Modelos Animales de Enfermedad , Proteínas Fluorescentes Verdes , Isquemia/terapia , Células Madre Mesenquimatosas/citología , Músculo Esquelético/irrigación sanguínea , Distribución Aleatoria , Ratas Sprague-Dawley , Trasplante Homólogo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Effects of three ions, Mn2+, Cu2+ and Zn2+ on biological treatment of pharmaceutical wastewater by a functional strain Xhhh were investigated. Through orthogonal tests, Cu2+ was determined to be the most important factor influencing Xhhh biodegradation performance. Biodegradation kinetic experiments demonstrated that with Cu2+concentration at about 2.00 mg l-1, the maximum of specific growth rate and specific degradation rate were obtained to be 0.033 and 0.075 d-1, respectively. The optimal levels of Mn2+ (5.00 mg l-1), Cu2+ (2.00 mg l-1) and Zn2+ (5.00 mgl -1) were achieved based on experimental results of their effects on the activities of manganese peroxidase and lignin peroxidase, and biodegradation kinetic parameters. Among three types of biodegradation kinetic models (Monod, Tessier and Contois), Tessier model was found most reasonable for kinetics description of Xhhh growth (R2 = 0.995) and pollutants degradation (R2 = 0.970) in the case of metals optimization. Both kinetics evaluation and experimental results demonstrated that optimization with the three metals made a great contribution to Xhhh growth and COD removal for pharmaceutical wastewater treatment.