Transcriptional changes in macrophages after engulfing human cord tissue mensenchymal stromal cells
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ABSTRACT:
PROVIDER: PRJNA630267 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11685393.fastq.gz | Fastqsanger.gz | |||
| SRR11685394.fastq.gz | Fastqsanger.gz | |||
| SRR11685395.fastq.gz | Fastqsanger.gz | |||
| SRR11685396.fastq.gz | Fastqsanger.gz | |||
| SRR11685397.fastq.gz | Fastqsanger.gz |
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Project description:Mesenchymal stromal cells (MSCs) with regenerative and immunomodulatory potential are being investigated as a potential therapeutic tool for cartilage lesions. MSCs express a wide variety of bioactive molecules including cytokines, trophic factors, and proteases, which act in a paracrine fashion to modulate the tissue microenvironment. Yet, little is known about the divergence of these signalling molecules between MSCs populations from adult or young tissues. This makes it challenging to decide the optimal source of MSCs for a specific clinical application. In this study, we investigated cell secretomes from cultured human stromal cells harvested from Hoffa’s fat pad (HFPSCs), synovial membrane (SMSCs), umbilical cord (UCSCs) and cartilage (ACs) by quantitative LC-MS/MS proteomics. We also performed multiplex protein arrays and functional assays to compare the constitutive immunomodulatory capabilities of different MSCs. Proteins involved in extracellular matrix degradation and inflammation such as MMPs, IL-17, and complement factors were significantly downregulated in UCSCs compared to other cell types. Additionally, we found enhanced expression of TGF-β1 and PGE2 in UCSCs supernatants. UCSCs were superior in inhibiting peripheral blood mononuclear cells proliferation, migration and TNF-α and IFN-γ secretion compared to ACs, HFPSCs and SMSCs. Although all cell types could repress HLA-DR surface expression and cytokine release by activated macrophages, only UCSCs significantly blocked IL-6 and IL-12 production. Our data demonstrate that stromal cells from umbilical cords display superior anti-inflammatory and immunosuppressive properties than stromal cells from adult tissues. This Allogeneic cell source could potentially be considered as an adjuvant therapy for articular cartilage repair.
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Project description:Epigenetic changes in umbilical cord mesenchymal stromal cells upon stimulation and culture expansion
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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.
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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).
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