AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of colitis.METHODS:MSCs were isolated from C57BL/6 mouse adipose tissue.MSC c...AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of colitis.METHODS:MSCs were isolated from C57BL/6 mouse adipose tissue.MSC cultures were analyzed according to morphology,cellular differentiation potential,and surface molecular markers.Experimental acute colitis was induced in C57BL/6 mice by oral administration of2%dextran sulfate sodium(DSS)in drinking water ad libitum from days 0 to 7.Colitis mice were treated with1×106 MSCs via intraperitoneal or intravenous injection on days 2 and 5.The disease activity index was determined daily based on the following parameters:weight loss,stool consistency and presence of blood in the feces and anus.To compare morphological and functional differences in tissue regeneration between different MSC injection modalities,mice were euthanized on day 8,and their colons were examined for length,weight,and histopathological changes.Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit.Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated d UDPbiotin nick end labeling assay.RESULTS:Intravenous infusion of MSCs was more effective than intraperitoneal treatment(P<0.001)in reducing the clinical and histopathologic severity of colitis,which includes weight loss,diarrhea and inflammation.An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells.This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)];and by the up-regulation of anti-inflammatory cytokines(IL-10 and IL-4).Intravenous transplantation alsoinduced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs,which did not occur with intraperitoneal transplantation(P=0.006).An increase in apoptotic T cells was observed after intravenous,but not intraperitoneal,MSC infusion,suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation(P=0.027).CONCLUSION:Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.展开更多
Resin infiltrants have been effectively applied in dentistry to manage non-cavitated carious lesions in proximal dental surfaces.However,the common formulations are composed of inert methacrylate monomers.In this stud...Resin infiltrants have been effectively applied in dentistry to manage non-cavitated carious lesions in proximal dental surfaces.However,the common formulations are composed of inert methacrylate monomers.In this study,we developed a novel resin infiltrant with microcapsules loaded with an ionic liquid(MC-IL),and analyzed the physical properties and cytotoxicity of the dental resin.First,the ionic liquid 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide(BMI.NTf2)was synthesized.BMI.NTf2 has previously shown antibacterial activity in a dental resin.Then,MC-IL were synthesized by the deposition of a preformed polymer.The MC-IL were analyzed for particle size and de-agglomeration effect via laser diffraction analysis and shape via scanning electron microscopy(SEM).The infiltrants were formulated,and the MC-IL were incorporated at 2.5%,5%,and 10 wt%.A group without MC-IL was used as a control.The infiltrants were evaluated for ultimate tensile strength(UTS),contact angle,surface free energy(SFE),and cytotoxicity.The MC-IL showed a mean particle size of 1.64(±0.08)μm,shriveled aspect,and a de-agglomeration profile suggestive of nanoparticles’presence in the synthesized powder.There were no differences in UTS among groups(p>0.05).The incorporation of 10 wt%of MC-IL increased the contact angle(p<0.05),while the addition from 5 wt%reduced the SFE in comparison to the control group(p<0.05).The human cell viability was above 90%for all groups(p>0.05).The incorporation of microcapsules as a drug-delivery system for ionic liquids may be a promising strategy to improve dental restorative materials.展开更多
基金Supported by Fundo de IncentivoàPesquisa e Eventos do Hospital de Clínicas de Porto Alegre and Coordenacao de Aperfeicoamento de Pessoal de Nível Superior
文摘AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of colitis.METHODS:MSCs were isolated from C57BL/6 mouse adipose tissue.MSC cultures were analyzed according to morphology,cellular differentiation potential,and surface molecular markers.Experimental acute colitis was induced in C57BL/6 mice by oral administration of2%dextran sulfate sodium(DSS)in drinking water ad libitum from days 0 to 7.Colitis mice were treated with1×106 MSCs via intraperitoneal or intravenous injection on days 2 and 5.The disease activity index was determined daily based on the following parameters:weight loss,stool consistency and presence of blood in the feces and anus.To compare morphological and functional differences in tissue regeneration between different MSC injection modalities,mice were euthanized on day 8,and their colons were examined for length,weight,and histopathological changes.Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit.Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated d UDPbiotin nick end labeling assay.RESULTS:Intravenous infusion of MSCs was more effective than intraperitoneal treatment(P<0.001)in reducing the clinical and histopathologic severity of colitis,which includes weight loss,diarrhea and inflammation.An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells.This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)];and by the up-regulation of anti-inflammatory cytokines(IL-10 and IL-4).Intravenous transplantation alsoinduced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs,which did not occur with intraperitoneal transplantation(P=0.006).An increase in apoptotic T cells was observed after intravenous,but not intraperitoneal,MSC infusion,suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation(P=0.027).CONCLUSION:Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.
基金This study was financed in part by the Coordenaçāo de Aperfeiçoamento de Pessoal de Nível Superior-Brasil(CAPES)-Finance Code 001,and Conselho Nacional de Desenvolvimento Científico e Tecnològico-Brasil(CNPq)-n◦307095/2016-9.
文摘Resin infiltrants have been effectively applied in dentistry to manage non-cavitated carious lesions in proximal dental surfaces.However,the common formulations are composed of inert methacrylate monomers.In this study,we developed a novel resin infiltrant with microcapsules loaded with an ionic liquid(MC-IL),and analyzed the physical properties and cytotoxicity of the dental resin.First,the ionic liquid 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide(BMI.NTf2)was synthesized.BMI.NTf2 has previously shown antibacterial activity in a dental resin.Then,MC-IL were synthesized by the deposition of a preformed polymer.The MC-IL were analyzed for particle size and de-agglomeration effect via laser diffraction analysis and shape via scanning electron microscopy(SEM).The infiltrants were formulated,and the MC-IL were incorporated at 2.5%,5%,and 10 wt%.A group without MC-IL was used as a control.The infiltrants were evaluated for ultimate tensile strength(UTS),contact angle,surface free energy(SFE),and cytotoxicity.The MC-IL showed a mean particle size of 1.64(±0.08)μm,shriveled aspect,and a de-agglomeration profile suggestive of nanoparticles’presence in the synthesized powder.There were no differences in UTS among groups(p>0.05).The incorporation of 10 wt%of MC-IL increased the contact angle(p<0.05),while the addition from 5 wt%reduced the SFE in comparison to the control group(p<0.05).The human cell viability was above 90%for all groups(p>0.05).The incorporation of microcapsules as a drug-delivery system for ionic liquids may be a promising strategy to improve dental restorative materials.
