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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

ORGANISM(S): Homo sapiens

PROVIDER: GSE23366 | GEO | 2010/08/03

SECONDARY ACCESSION(S): PRJNA131243

REPOSITORIES: GEO

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Project description:GENES ASSOCIATED WITH THE CELL CYCLE, LINEAGE COMMITMENT AND IMMUNOMODULATORY POTENTIAL DISCRIMINATE HUMAN POSTNATAL STEM CELLS OF DIFFERENT ORIGIN. Stem cells hold great promise for future clinical use. Their intrinsic biological properties are, however, not fully understood and many of their therapeutic benefits still unclear. Better understanding of their genetic and biological properties is essential for the development of clinically relevant stem cell applications. The neonatal unrestricted somatic stem cell (USSC) from cord blood has the capacity to differentiate into cells from all three germ layers. Here we investigate the gene expression profile of USSC using the Affymetrix Exon Array platform and compare it with those of bone-marrow derived mesenchymal adult stem cells (BM-MSC) and adipose tissue-derived adult stem cells (AdAS). Extensive data analysis revealed limited variation in the expression profile of the different cell lines from the same origin, while stem cells from different origins showed distinct profiles, with the BM-MSC and AdAS being more closely related to each other than to USSC. Interestingly, USSC expressed genes involved in the cell cycle at much higher levels, indicative of their relatively higher cycling rate (~ 24 hrs as opposed to more than 2 days for BM-MSC and AdAS). They also show higher expression of genes involved in neurogenesis, consistent with their reported neuronal differentiation capacity. The BM-MSC signature indicates that they are primed towards developmental processes of tissues and organs derived from the mesoderm and endoderm. Remarkably, AdAS appear to be highly enriched in immune-related genes. Together, the data suggest that the different mesenchymal stem cell types have distinct gene expression profiles,that reflect their origin and differentiation potential. Keywords: Adult stem cells, developmental biology, gene expression, genomics, human cord blood, mesenchymal stem cells, cell type comparison

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Cord blood multipotent stromal cells exploit a unique immune suppressive mechanism

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