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1.
Wound Repair Regen ; 23(6): 830-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26053405

RESUMO

Oxygen generating biomaterials represent a new trend in regenerative medicine that aims to generate and supply oxygen at the site of requirement, to support tissue healing and regeneration. To enhance the healing of dermal wounds, we have developed a highly portable, in situ oxygen generating wound dressings that uses sodium percarbonate (SPO) and calcium peroxide (CPO) as chemical oxygen sources. The dressing continuously generated oxygen for more than 3 days, after which it was replaced. In the in vivo testing on porcine full-thickness porcine wound model, the SPO/CPO dressing showed enhanced wound healing during the 8 week study period. Quantitative measurements of wound healing related parameters, such as wound closure, reepithelialization, epidermal thickness and collagen content of dermis showed that supplying oxygen topically using the SPO/CPO dressing significantly accelerated the wound healing. An increase in neovascularization, as determined using Von Willebrand factor (vWF) and CD31 staining, was also observed in the presence of SPO/CPO dressing. This novel design for a wound dressing that contains oxygen generating biomaterials (SPO/CPO) for supplying topical oxygen, may find utility in treating various types of acute to chronic wounds.


Assuntos
Bandagens , Oxigênio/farmacologia , Peróxidos/farmacologia , Regeneração , Lesões dos Tecidos Moles/patologia , Cicatrização , Administração Tópica , Animais , Materiais Biocompatíveis , Modelos Animais de Doenças , Neovascularização Fisiológica , Medicina Regenerativa , Suínos , Cicatrização/efeitos dos fármacos
2.
J Crohns Colitis ; 14(5): 654-668, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31841595

RESUMO

BACKGROUND AND AIMS: Despite the therapeutic promise of stem cell therapy in the treatment of inflammatory bowel diseases [IBD], most donor cell populations have to be obtained via invasive approaches and often remain insufficiently validated. Urine-derived stem cells [USC] were recently shown to have regenerative properties and can be harvested in a safe, low-cost, and noninvasive way. This study aims to evaluate the immunomodulatory effect of USC and their efficacy in the management of IBD. METHODS: Human USC were isolated and expanded from the urine of healthy male adult volunteers [n = 3, age range 24-30 years]. USC were characterised by cell surface marker expression profile and multipotent differentiation. The in vitro immunomodulatory effect of USC was evaluated by co-culturing with human CD4+ T cells upon stimulation with phytohaemagglutinin [PHA]. The proliferation of CD4+ T was measured by fluorescence-activated cell sorting [FACS]. Cytokine array and quantitative real-time polymerase chain reaction [RT-PCR] were applied to examine cytokine levels. In vivo therapeutic value of USC was assessed using a murine colitis model induced by dextran sulphate sodium [DSS] or 2, 4, 6-trinitrobenzene sulphonic acid [TNBS]. The immunomodulatory effect of USC and bone marrow-derived mesenchymal stem cells [BMSC] was compared when co-cultured with CD4+ T cells. The therapeutic efficacy of USC and BMSC on IBD was compared when administered in an acute DSS model in vivo. RESULTS: USC were positive for mesenchymal stem cell markers but were negative for haematopoietic stem cell markers. These cells differentiated into osteo-, adipo-, and chondrogenic cell lineages. Similar to BMSC, the proliferation of CD4+ T cells was significantly inhibited when co-cultured with USC, as a consequence of Th1/Th17 immune response inhibition. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in both acute and chronic murine colitis models. Moreover, implantation of USC led to downregulation of the Th1/Th17 immune responses in a PGE2-dependent manner. CONCLUSIONS: This study demonstrated that implantation of USC reduces inflammation in an IBD rodent model via downregulation of Th1/Th17 immune responses, indicating that USC therapy serves as a potential cell-based therapeutic candidate treatment for IBD.


Assuntos
Colite/terapia , Dinoprostona/metabolismo , Imunomodulação , Doenças Inflamatórias Intestinais/imunologia , Células-Tronco/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adulto , Animais , Células da Medula Óssea/imunologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Colite/induzido quimicamente , Colite/patologia , Colite/fisiopatologia , Ciclo-Oxigenase 2/genética , Citocinas/genética , Citocinas/metabolismo , Sulfato de Dextrana , Dinoprostona/genética , Regulação para Baixo/imunologia , Técnicas de Silenciamento de Genes , Humanos , Doenças Inflamatórias Intestinais/terapia , Ativação Linfocitária , Masculino , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fito-Hemaglutininas/farmacologia , Transplante de Células-Tronco , Células-Tronco/fisiologia , Ácido Trinitrobenzenossulfônico , Urina/citologia , Adulto Jovem
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