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Eradication of donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance their therapeutic values.

ABSTRACT: Eradication of donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance their therapeutic values.

PROVIDER: PRJNA697955 | ENA |

REPOSITORIES: ENA

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Eradication of donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance their therapeutic values.

Project description:Mesenchymal stem cells (MSC) are one of the most widely clinically trialed stem cells, due to their abilities to secret regenerative/rejuvenating factors, modulate immune functions, among others. In this study, we analyzed human umbilical-cord-derived MSC from 32 donors and revealed donor-dependent variations in two non-correlated properties, 1) cell proliferation, and 2) immune modulatory functions in vitro and in vivo, which might explain inconsistent clinical efficacies of MSC. Through unbiased transcriptomic analyses, we discovered that IFN- γ and NF-κB signaling were positively associated with immune modulatory function of MSC. Activation of these two pathways via IFN-γ and TNF-α treatment eradicated donor-dependent variations. Additional transcriptomic analyses revealed that treatment with these two factors, while abolished donor-dependent variations in immune modulatory function, did not overall made different donor-derived MSC more similar at whole transcriptomic levels, meaning the cells were still different in many other biological perspectives, and might not perform equally for therapeutic purposes other than immune modulation. Pre-selection or pre-treatment to eradicate MSC variations in a disease-treatment-specific manner would therefore be necessary to assure clinical efficacies. Together this study provided novel insights into the quality control perspective of using different-donor-derived MSC to treat inflammation-related clinical conditions and/or autoimmune diseases.

2021-02-01 | GSE165811 | GEO

Eradication of specific donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance therapeutic values.

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immunomodulation via human enteric viruses

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Worms spun in centrifuge at elevated g values

Project description:Worms spun at higher than normal g values for 4 days on 20G centrifuge vs. worms kept at 1 X G. Both are mixed stage cultures. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Physical Characteristics: worms kept at increased g values for 4 days (x g value)

2013-06-22 | GSE38877 | GEO

Single-cell transcriptome analysis of stem cells from human exfoliated deciduous teeth investigating functional heterogeneity in immunomodulation

Project description:Background: Mesenchymal stem cells (MSCs) have been widely used in the treatment of various inflammatory diseases. The inadequate understanding of MSCs and its heterogeneity can impact the immune environment maybe the cause of the good outcomes of MSCs-based therapy cannot be always achieved. Recently, stem cells from human exfoliated deciduous teeth (SHED) showed a great potential in inflammatory and autoimmune diseases due to its unique immunomodulation properties. However, the cellular heterogeneity and the corresponding immunomodulation functions of SHED remains unclear. Methods: In this study, we applied single-cell RNA sequencing (scRNA-seq) to analyze and performed bioinformatic analysis to clarify the variations immunomodulation functions of SHED subpopulations in different differentiation state. After the integration of public available databases, we analyzed the transcriptome and compared the difference of immunomodulation functions of MSCs from different tissues. Results: SHED in low differentiation state (S7) exhibited the powerful ability to recruit multiple types of immune cells, whereas SHED in relatively high differentiation state (S1) may hold strong ability to secret many factors with paracrine signaling capacity. Compared with human bone marrow derived mesenchymal stem cells (hBMSCs) or human umbilical cord-derived mesenchymal stem cells (hUCMSCs), SHED is stronger in immunomodulatory property, especially in recruitment of Th17, Th22 and Treg cells. Conclusion: SHED was a heterogeneous MSCs population with different differentiation states and immunomodulatory functions. SHED may have some advantages in treatment of inflammatory and autoimmune diseases. Our works provides some theoretical foundation for the SHED-based therapy in clinical applications.

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Effect of Helicobacter pyroli eradication on colorectal cancer inhibition

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Selective eradication of leukemia cells with reprogramming factors

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A Novel Gene Regulates Vesiculogenesis and Immunomodulation in Mycobacterium tuberculosis

Project description:After co-evolving with humans, its only major host, Mycobacterium tuberculosis (Mtb) restrains immune responses well enough to escape eradication, yet elicits enough immunopathology to ensure its transmission. Here, we provide evidence that this balance is regulated in part by a previously uncharacterized, cytosolic, membrane-associated protein with a novel structural fold, encoded by the Mtb gene rv0431. The protein acts by regulating the quantity and quality of Mtb-derived membrane vesicles bearing TLR2 ligands, including the lipoproteins LpqH and SodC. We propose that rv0431 be named virR (vesiculogenesis and immune response regulator). To our knowledge, VirR is the first bacterial protein identified to regulate vesiculogenesis. Transcriptome sequencing of mouse macrophages uninfected, infected with WT Mtb, or infected with rv0431 mutant Mtb.

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Synthetic immunomodulation with a CRISPR super-repressor in vivo

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