RESUMEN
The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73+Foxp3+Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.
Asunto(s)
Redes Reguladoras de Genes , Metaloproteinasa 9 de la Matriz/metabolismo , Células Madre Mesenquimatosas/citología , Linfocitos T Reguladores/citología , Adulto , Anciano , Proliferación Celular , Células Cultivadas , Femenino , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Linfocitos T Reguladores/metabolismoRESUMEN
The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-gamma and TNF-alpha production, along IL-10 increase, (ii) CD73(+) Foxp3(+) Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.
RESUMEN
Este estudo irá relatar o caso de uma criança portadora de cardiopatia congênita cianótica que compreende cuidados de enfermagem complexos e específicos. A prática diária numa unidade de terapia intensiva pediátrica junto às crianças portadoras deste tipo de anomalia, exige uma equipe de enfermagem especializada e qualificada, que deve direcionar seus cuidados com um conhecimento técnico-científico. Para o interesse deste estudo, destacamos a atuação do enfermeiro pediátrico frente ao cuidado integrado e sistematizado no pós-operatório de um recém-nascido de baixo peso na correção da transposição das grandes artérias (TGA).
This study reports the case of a newborn with congenital heart disease (transposition of the great arteries[TGA]) demanding complex and specific treatment. In a Pediatric Intensive Care Unit(ICU), the daily practice with children having this category of anomalies demands a properly qualified nursing staff driving the care with technical and scientific knowledge. This study focus the pediatric nursing actions taken on the integrated treatment during postoperatory of a low-weight newborn submitted to corrective surgery.