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 Dendritic cells co cultured with cord blood MSC compared with cord blood MSC (USSC).
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
Project description:Unrestricted somatic stem cells (USSCs) from human cord blood show distinct differences to multipotent stromal cells isolated from human bone marrow and placenta both at the gene array and functional level. Fibroblast samples and raw data also included in E-TABM-724.
Project description:The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host and highlight the plasticity of the fetal immune system following viral exposure in utero. RNA was extracted from 15 cord blood samples comprising of healthy cord blood monocytes (n=4), HBV-exposed cord blood monocytes (n=3), healthy cord blood plasmacytoid dendritic cells (n=4), and HBV-exposed cord blood plasmacytoid dendritic cells (n=4). Healthy adult peripheral blood monocytes (n=3) were included for comparison. The immune profile was analyzed using Nanostring and nCounter® GX Human Immunology Kit v1, comprising probes for a total of 511 immune genes.
Project description:Circulating osteoprogenitor (COP) are a population of cell in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). While there is functional overlap, it is not known how COP cells are related to bone marrow (BM)-derived MSCs (BM-MSCs) and other better characterized stromal progenitor populations such as adipose-derived stromal cells (ASCs). This study compares COP cells to BM-MSCs and ASCs through detailed transcriptomic and proteomic analyses. COP cells have a distinct gene and protein expression pattern to BM-MSCs and ASCs, with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. However, they also have a similar pattern of expression BM-MSCs and ASCs, in genes and proteins in progenitor cell differentiation and proliferation pathways. This study shows COP cells to be a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, but with a strong immune phenotype, with potential for translational regenerative medicine strategies.
Project description:Umbilical cord blood banking is critical for the success of umbilical cord blood transplants. Here we analyzed transcriptomic differences between 27-year cryopreserved umbilical cord blood hematopoietic stem cells (HSCs) and multipotent progenitor cells (MPPs) and those derived from fresh cord blood. We also leveraged differences in engraftment capacity to examine the transcriptomes of HSCs/HPCs defined by engraftment capacity, demonstrating the feasibility of this approach for identifying potency markers to aid in the selection of cord blood units for transplantation and revealing novel potential regulators of cord blood HSC/HPC engraftment.
Project description:Global gene expression analysis of (a) human embryonic stem cells, (b) adult fibroblasts with and without nucleofection of SOKM, (c) CD34+ cord blood cells at various time points during induction of pluripotency with SOKM, with or without co-culture with bone marrow stromal cells (BMSC), and (d) resulting stromal primed and non-stromal primed cord blood CD34+ myeloid iPSC
Project description:In homeostasis, because of the blood-brain barrier, immune cells rarely infiltrate the central nervous system (CNS). However, after spinal cord injury (SCI), many cells, including both myeloid and T cells, infiltrate the spinal cord. However, the role immune cells play in SCI remains controversial. We are curious whether after SCI there are self-peptides that are released and sensed by T cells that then modulate response to CNS injury.
Project description:Mesenchymal stromal cells (MSCs) are multipotent progenitors that can be isolated from different sources, such as the bone marrow, adipose tissue and umbilical cord. The therapeutic potential of MSCs is related to a plethora of immunomodulatory, anti-inflammatory and pro-repair actions, which are at least partially dependent on their secretome. Among the components of MSCs' secretome, EVs have received considerable attention because MSC-EVs exert similar therapeutic properties as their parent cells. Among the different MSC sources for EV production, human umbilical cord MSCs (hUCMSCs) show advantages such as tissue availability, high proliferative profile of the cells and potential beneficial therapeutic effects in a variety of different diseases, such as stroke This study aimed to provide novel insights for future hUCMSC-EVs research and treatment selection. We investigated the influence of the culture and harvesting conditions on the EV proteomic profile, productivity, surface markers expression and evaluated their in vivo biodistribution and toxicity.