Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Front Immunol ; 11: 575488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117373

RESUMO

Mesenchymal stromal cells (MSC) have been used in over 800 clinical trials with encouraging results in the field of transplant medicine and chronic inflammatory diseases. Today, Umbilical Cord (UC)-derived MSC are the second leading source used for clinical purposes, mainly due to its easy access and superior immune modulatory effects. Although the underlying molecular mechanisms of immune suppressive activities have not been fully understood, research over the last decade strongly suggests that MSC-mediated benefits are closely related to activation of secretome networks. Nevertheless, recent findings also point to cytokine-independent mechanisms as key players of MSC-mediated immune modulation. Here, we set up a robust in vitro immune assay using phytohemagglutinin- or anti-CD3/CD28-treated human peripheral blood mononuclear cells in cell-to-cell interaction or in cell-contact independent format with UC-MSC and conducted integrated transcriptome and secretome analyses to dissect molecular pathways driving UC-MSC-mediated immune modulation. Under inflammatory stimuli, multiparametric analyses of the secretome led us to identify cytokine/chemokine expression patterns associated with the induction of MSC-reprogrammed macrophages and T cell subsets ultimately leading to immune suppression. UC-MSC transcriptome analysis under inflammatory challenge allowed the identification of 47 differentially expressed genes, including chemokines, anti- and pro-inflammatory cytokines and adhesion molecules found also in UC-MSC-immunosupressive secretomes, including the novel candidate soluble IL-2R. This study enabled us to track functionally activated UC-MSC during immune suppression and opened an opportunity to explore new pathways involved in immunity control by UC-MSC. We propose that identified immunomodulatory molecules and pathways could potentially be translated into clinical settings in order to improve UC-MSC-therapy quality and efficacy.


Assuntos
Inflamação/metabolismo , Células-Tronco Mesenquimais/metabolismo , Comunicação Parácrina , Linfócitos T/metabolismo , Transcriptoma , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Citocinas/genética , Citocinas/metabolismo , Sangue Fetal/citologia , Redes Reguladoras de Genes , Humanos , Inflamação/genética , Inflamação/imunologia , Ativação Linfocitária , Células-Tronco Mesenquimais/imunologia , Fenótipo , Via Secretória , Transdução de Sinais , Linfócitos T/imunologia
2.
Int J Mol Sci ; 20(19)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575081

RESUMO

Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34+ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34+ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34+ cell count significantly impacted CD34+ viability after thawing, along with HLA-B or -C (R2 = 0.95, p = 0.01; R2 = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34+ cell viability, RBC depletion significantly improves it.


Assuntos
Comunicação Celular , Eritrócitos/metabolismo , Sangue Fetal/citologia , Antígenos HLA/genética , Células-Tronco Hematopoéticas/metabolismo , Alelos , Antígenos CD34/metabolismo , Comunicação Celular/genética , Sobrevivência Celular/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Criopreservação , Células-Tronco Hematopoéticas/citologia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA