Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Front Immunol ; 4: 203, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23882269

RESUMO

Adipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The function of ASC adapts to environmental conditions, such as oxygen tension. Oxygen levels within tissues are typically much lower than under standard culture conditions and ASC used for therapy therefore encounter a change from normoxic to hypoxic conditions. The effect of hypoxia on the regenerative potential of ASC has been investigated in a number of studies. The effect of hypoxia on the immunomodulatory function of ASC, however, remains to be determined. In the present study the effect of hypoxic (1% oxygen) culture conditions on human ASC was examined. ASC showed no signs of toxicity under low oxygen levels and no major immunophenotypical changes were observed, apart from a down regulation of the marker CD105. Oxygen tension had no effect on the proliferation of ASC and colony forming unit efficiency remained the same under 1 and 20% oxygen. Under both oxygen levels ASC were capable of strong upregulation of the immunomodulatory molecules indoleamine 2,3-dioxygenase (IDO) and programed death ligand-1 upon stimulation with IFN-γ and TNF-α, and, in addition, IDO activity as measured by the accumulation of l-kynurenine was not affected under hypoxia. The ability of ASC to inhibit anti-CD3/CD28 stimulated CD4(+) and CD8(+) T cell proliferation was not hampered by hypoxia. The results of the present study demonstrate that the immunosuppressive capacity of ASC is maintained under hypoxic conditions. These findings are important for the therapeutic use of ASC and may be applied for the in vitro generation of ASC with improved functionality for therapeutic use.

2.
Stem Cells Dev ; 22(21): 2825-35, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23767885

RESUMO

Mesenchymal stem cells (MSCs) have potent immunosuppressive effects in vitro and are considered as a therapeutic option for autoimmune disease and organ transplantation. While MSCs show beneficial effects on immune disease progression and transplant survival in animal models, the immunomodulatory mechanisms involved are largely unknown. In the present study, we show that intravenously infused C57BL/6- green fluorescent protein (GFP) MSCs home to the lungs in C57BL/6 recipient mice and induce an inflammatory response. This response was characterized by increased mRNA expression of monocyte chemoattractant protein-1 (MCP1), IL1-ß, and TNF-α and an increase in macrophages in lung tissue 2 h after MSC infusion. Simultaneously, serum levels of proinflammatory IL6, CXCL1, and MCP1 protein increased, demonstrating systemic immune activation after MSC infusion. In liver tissue, no C57BL/6-GFP MSCs were detected, but MCP1 and TNF-α mRNA levels peaked 4 h after MSC infusion. The expression of the anti-inflammatory cytokines TGF-ß, IL4, and IL10 was only marginally affected. Nevertheless, 3 days after MSC infusion, animals developed a milder inflammatory response to lipopolysaccharides. Our results suggest that the in vivo immunomodulatory effects of MSCs originate from an inflammatory response that is induced by the infusion of MSCs, which is followed by a phase of reduced immune reactivity.


Assuntos
Quimiocinas/imunologia , Citocinas/imunologia , Pulmão/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Tecido Adiposo/citologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quimiocinas/sangue , Quimiocinas/genética , Citocinas/sangue , Citocinas/genética , Expressão Gênica/imunologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Infusões Intravenosas , Rim/imunologia , Rim/metabolismo , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , Fígado/imunologia , Fígado/metabolismo , Pulmão/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Fatores de Tempo
3.
Kidney Int ; 82(7): 748-58, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22695328

RESUMO

Mesenchymal stem cells are a potential therapeutic agent in renal disease and kidney transplantation. Autologous cell use in kidney transplantation is preferred to avoid anti-HLA reactivity; however, the influence of renal disease on mesenchymal stem cells is unknown. To investigate the feasibility of autologous cell therapy in patients with renal disease, we isolated these cells from subcutaneous adipose tissue of healthy controls and patients with renal disease and compared them phenotypically and functionally. The mesenchymal stem cells from both groups showed similar morphology and differentiation capacity, and were both over 90% positive for CD73, CD105, and CD166, and negative for CD31 and CD45. They demonstrated comparable population doubling times, rates of apoptosis, and were both capable of inhibiting allo-antigen- and anti-CD3/CD28-activated peripheral blood mononuclear cell proliferation. In response to immune activation they both increased the expression of pro-inflammatory and anti-inflammatory factors. These mesenchymal stem cells were genetically stable after extensive expansion and, importantly, were not affected by uremic serum. Thus, mesenchymal stem cells of patients with renal disease have similar characteristics and functionality as those from healthy controls. Hence, our results indicate the feasibility of their use in autologous cell therapy in patients with renal disease.


Assuntos
Tecido Adiposo/metabolismo , Nefropatias/metabolismo , Células-Tronco Mesenquimais/metabolismo , 5'-Nucleotidase/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Adulto , Idoso , Antígenos CD/metabolismo , Apoptose , Biomarcadores/metabolismo , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais/metabolismo , Diferenciação Celular , Proliferação de Células , Separação Celular/métodos , Forma Celular , Células Cultivadas , Técnicas de Cocultura , Endoglina , Feminino , Proteínas Fetais/metabolismo , Citometria de Fluxo , Proteínas Ligadas por GPI/metabolismo , Regulação da Expressão Gênica , Humanos , Imunofenotipagem/métodos , Mediadores da Inflamação/metabolismo , Nefropatias/sangue , Nefropatias/imunologia , Nefropatias/patologia , Antígenos Comuns de Leucócito/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Fenótipo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores de Superfície Celular/metabolismo , Fatores de Tempo , Transplante Autólogo , Uremia/sangue , Uremia/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA