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Cord blood multipotent stromal cells exploit a unique immune suppressive mechanism

ABSTRACT: Expression patterns of Dendritic cells co cultured with cord blood MSC were compared with cord blood MSC (USSC). Putative immune suppressive candidates were tested to explain this inhibition. We find that cord blood MSC themselves are hardly immunogenic as tested with allogeneic T-cells. Dendritic cells cocultured with second party T-cells evoked abundant proliferation that was inhibited by third party cord blood USSC. Optimal inhibition was seen with one cord blood USSC for every dendritic cell. Blocking HLA-G only saw partial recovery of proliferation. Several cytokines, prostaglandins, gangliosides, enzymes like arginase, NO synthase and indole amine 2,3-dioxygenase as well as the induction of Treg were not involved in the inhibition based on the microarrays and functional tests. Although the mechanism by which it does so remains partially undefined and subject to further study, cord blood multipotent stromal cells are strong inhibitors of the immune response and therefore allow their use in tissue regeneration settings in an allogeneic setting. Keywords: Adult stem cells, developmental biology, gene expression, genomics, human cord blood, mesenchymal stem cells, cel type comparison Dendritic cells co cultured with cord blood MSC compared with cord blood MSC (USSC).

ORGANISM(S): Homo sapiens

SUBMITTER: Ruurd Torensma

PROVIDER: E-GEOD-23366 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cord blood multipotent stromal cells exploit a unique immune suppressive mechanism

Project description:Expression patterns of Dendritic cells co cultured with cord blood MSC were compared with cord blood MSC (USSC). Putative immune suppressive candidates were tested to explain this inhibition. We find that cord blood MSC themselves are hardly immunogenic as tested with allogeneic T-cells. Dendritic cells cocultured with second party T-cells evoked abundant proliferation that was inhibited by third party cord blood USSC. Optimal inhibition was seen with one cord blood USSC for every dendritic cell. Blocking HLA-G only saw partial recovery of proliferation. Several cytokines, prostaglandins, gangliosides, enzymes like arginase, NO synthase and indole amine 2,3-dioxygenase as well as the induction of Treg were not involved in the inhibition based on the microarrays and functional tests. Although the mechanism by which it does so remains partially undefined and subject to further study, cord blood multipotent stromal cells are strong inhibitors of the immune response and therefore allow their use in tissue regeneration settings in an allogeneic setting. Keywords: Adult stem cells, developmental biology, gene expression, genomics, human cord blood, mesenchymal stem cells, cel type comparison

2010-08-03 | GSE23366 | GEO

Effect of MSC and MSC-derived extracellular vesicles on human blood coagulation

Project description:Mesenchymal stem cells (MSC) have emerged as potent therapeutic tool for a number of pathologies, including immune ones. However, unwelcome effects of MSC on the blood coagulation were revealed in some cases, which require more in-depth analysis. In this study, we explored the trombotic properties of human MSC from umbilical cord. We revealed strong procoagulant effects of umbilical cord MSC toward human and rat whole blood and platelets-free plasma using rotational thromboelastometry and thrombodynamics tests. The similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EV). In order to suggest approaches to avoid unwanted effects we studied the impact of heparin supplement on MSC/EV procoagulation properties. We found that therapeutic doses of unfractionated heparin injected in the patient's blood (administered in vivo) did not abrogate the procoagulant properties of MSC. Mass-spectrometry analysis of proteins of MSC and EV involved in coagulation-associated pathways was used to evaluate mechanisms of protrombotic effects.

2019-03-26 | PXD012768 | Pride

Mesenchymal stromal cells perturb human monocyte in vitro differentiation into dendritic cells

Project description:Monocytes cultured in media containing GM-CSF and IL4 for 5 days normally differentiate into immature dendritic cells which, upon further stimulation with LPS for an additional 2 days, acquire a mature phenotype. In the present study, we evaluated the effect of human cord-blood mesenchymal stem cells (MSC) on human monocyte differentiation into immature and mature DCs by examining the trancriptional profile of the cells that were obtained after both the differentiation and maturation stages.

2016-05-09 | GSE68962 | GEO

Expression data of Mesenchymal Stroma Cells (MSC)-adherent and non-adherent, human cord blood-derived, hematopoietic CD34 cells

Project description:MSC-adherent hematopoietic stem and progenotir cells (HSPC) express adhesion-associated genes at higher levels than non-adherent cells while cell-cycle and differentiation-associated genes are not significantly changed between the two cell populations. We used microarray to confirm identity of MSC-adherent and non-adherent cord blood-derived HSPCs and to exclude that cell cycle and differentiation affect adhesive capacity. CD34 positive cells were isolated from human cord blood (not older than 24h), expanded for 3 days and assayed for the adhesion to MSC. The adherent and non-adherent live CD34+ cells were sorted and total RNA was extracted.

2016-05-16 | E-GEOD-78216 | biostudies-arrayexpress

Molecular and functional characterization of alloantigen-specific anergic T-cell suitable for cell therapy

Project description:IL-10 is an immunomodulant cytokine that plays a central role in controlling inflammation, down-regulating immune responses, and inducing immunological tolerance. IL-10 inhibits the expression of costimulatory molecules and the secretion of inflammatory cytokines by antigen-presenting cells (APC), directly suppresses T-cell proliferation, and promotes T-cell anergy. In this study we demonstrate that IL-10 inhibits primary allogeneic proliferation in total PBMC and induces antigen(Ag)-specific T-cell hyporesponsiveness. IL-10-induced anergy is TGF-beta independent, is associated with a decrease of Ag-specific CTLp frequency, and can be obtained among cells with different degree of HLA disparity. The use of tolerogenic dendritic cells (DC) differentiated in the presence of IL-10 (DC-10) allows a more consistent anergy induction, even in the context of HLA matched donors. Importantly, alloAg-IL-10/DC-10-anergized T cells preserve their ability to respond to nominal and third party Ags. Microarray experiments were conducted on different mixed lymphocyte cultures aiming at the identification of gene expression profiles characteristic for the various T cell populations. Independently from the APC used to anergized T cells, the resulting T cell populations exhibit a specific gene signature. Based on the results of this study, we developed a method suitable for GMP scale up and for the generation of a population of anergic Ag-specific T cells for cellular therapy. The dataset comprises 12 samples divided into four sample groups each representing a certain kind of allogeneic mixed lymphocyte culture, i.e. peripheral blood mononuclear cells (PBMC) mixed with CD3-depleted cells (MEC, monocyte-enriched cells) with or without IL-10 treatment, and PBMC mixed with mature or IL-10 treated dendritic cells (DCs). Each group includes three biological replicates with cells collected from different donors.

2010-08-16 | E-GEOD-17493 | biostudies-arrayexpress

Single-cell RNA-seq of human blood dendritic cells from buffy coats and in vitro differentiated dendritic cells from cord blood CD34 + stem cells

Project description:To compare human dendritic cells from peripheral blood, in vitro cultures with dendritic cells from human tumor tissues in publicly available single-cell RNA-seq datasets we performed single-cell RNA-seq of human blood dendritic cells and in vitro differentiated dendritic cells from cord blood CD34 + stem cells

2022-06-15 | E-MTAB-11735 | biostudies-arrayexpress

Hematopoietic Progenitor Cells of Different Donor Age

Project description:In this series we have analyzed the effect of donor age on the gene expression profile of human hematopoietic stem and progenitor cells (HPC). Cells were taken from umbilical cord blood (CB) or from G-CSF mobilized blood of healthy donors for allogeneic blood stem cell transplantation.

2009-06-12 | GSE12277 | GEO

Transcriptional profile of human neonatal cord blood and adult peripheral blood dendritic cells

Project description:A phenotypically and functinoally distinct subset of human blood dendritic cells expressing CD11b is specific of the neonatal environment. We have employed whole genome microarray expression profiling to identify the specific gene signature of CD11b+ cord blood dendritic cells as compared to their adult peripheral blood counterparts. Peripheral blood adult cDC2 (CD20- CD11c+ CD14- BDCA1+ CD11b- ), neonatal cord blood cDC2 (CD20- CD11c+ CD14- BDCA1+ CD11b-) and neonatal cord blood cDC2b (CD20- CD11c+ CD14- BDCA1+ CD11b+) were FACS purified from BDCA1+ magnetically. Neonatal monocytes (CD11c+ CD14+) and neonatal naive T cells (CD3+ CD4+ CD56- CD25- CD45RO-) were used as controls.

2018-09-21 | GSE104110 | GEO

Gene expression profile of mesenchymal stem cells from paired umbilical cord units: cord is different from blood

Project description:Mesenchymal stem cells (MSC) are multipotent cells which can be obtained from several adult and fetal tissues including human umbilical cord units. We have recently shown that umbilical cord tissue (UC) is richer in MSC than umbilical cord blood (UCB) but their origin and characteristics in blood as compared to the cord remains unknown. Here we compared, for the first time, the exonic protein-coding and intronic noncoding RNA (ncRNA) expression profiles of MSC from match-paired UC and UCB samples, harvested from the same donors, processed simultaneously and under the same culture conditions. The patterns of intronic ncRNA expression in MSC from UC and UCB paired units were highly similar, indicative of their common donor origin. The respective exonic protein-coding transcript expression profiles, however, were significantly different. Hierarchical clustering based on protein-coding expression similarities grouped MSC according to their tissue location rather than original donor. Genes related to systems development, osteogenesis and immune system were expressed at higher levels in UCB, whereas genes related to cell adhesion, morphogenesis, secretion, angiogenesis and neurogenesis were more expressed in UC cells. These molecular differences verified in tissue-specific MSC gene expression may reflect functional activities influenced by distinct niches and should be considered when developing clinical protocols involving MSC from different sources. In addition, these findings reinforce our previous suggestion on the importance of banking the whole umbilical cord unit for research or future therapeutic use.

2009-09-18 | GSE18134 | GEO

Progesterone-regulated genes in immune cells: Regulation of T cell genes by progesterone

Project description:We examined the global gene expression pattern of T cells regulated by progesterone to gain further insights into the regulatory mechanisms of progesterone. We found 325-347 cord blood T cell genes up or down-regulated by P4 in the presence or absence of exogenous TGFb1. Peripheral blood T cells were relatively unresponsive with only 30-70 genes regulated by P4. IL-6 receptor (IL-6R) expression was greatly down-regulated by progesterone in cord blood, but not PB, T cells. Overall, these differences in gene expression are consistent with the differential responses of cord blood and peripheral blood T cells to progesterone. To gain insights into the differences of progesterone and control dendritic cells, we performed a microarray study and found ~180 genes regulated by progesterone in dendritic cells. The gene expression information suggests that progesterone has the potential to alter dendritic cell responses to cytokines, chemokine production, and migration which in combination would control T cell differentiation. The CD4+ CD25- T cells were isolated from cord blood and peripheral blood and cultured in the presence and absence of progesterone 2 ug per mL, TGFb1 150 pg/mL and IL-2 100u/mL for 5-6 days. T cells from cord blood and peripheral blood were compared.

2012-03-02 | E-GEOD-22025 | biostudies-arrayexpress

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