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Nestin⁺ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function.

ABSTRACT: Mesenchymal stromal cells (MSCs) are known to be widespread in many tissues and possess a broad spectrum of immunoregulatory properties. They have been used in the treatment of a variety of inflammatory diseases; however, the therapeutic effects are still inconsistent owing to their heterogeneity. Spleen stromal cells have evolved to regulate the immune response at many levels as they are bathed in a complex inflammatory milieu during infection. Therefore, it is unknown whether they have stronger immunomodulatory effects than their counterparts derived from other tissues. Here, using a transgenic mouse model expressing GFP driven by the Nestin (Nes) promoter, Nes-GFP⁺ cells from bone marrow and spleen were collected. Artificial lymphoid reconstruction in vivo was performed. Cell phenotype, inhibition of T cell inflammatory cytokines, and in vivo therapeutic effects were assessed. We observed Nes-GFP⁺ cells colocalized with splenic stromal cells and further demonstrated that these Nes-GFP⁺ cells had the ability to establish ectopic lymphoid-like structures in vivo. Moreover, we showed that the Nes-GFP⁺ cells possessed the characteristics of MSCs. Spleen-derived Nes-GFP⁺ cells exhibited greater immunomodulatory ability in vitro and more remarkable therapeutic efficacy in inflammatory diseases, especially inflammatory bowel disease (IBD) than bone marrow-derived Nes-GFP⁺ cells. Overall, our data showed that Nes-GFP⁺ cells contributed to subsets of spleen stromal populations and possessed the biological characteristics of MSCs with a stronger immunoregulatory function and therapeutic potential than bone marrow-derived Nes-GFP⁺ cells.

SUBMITTER: Huang J

PROVIDER: S-EPMC9569994 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Nestin<sup>+</sup> Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function.

Huang Jing J Deng Ronghai R Li Weiqiang W Jiang Meihua M Xiang Andy Peng AP Zhang Xiaoran X

International journal of molecular sciences 20221005 19

Mesenchymal stromal cells (MSCs) are known to be widespread in many tissues and possess a broad spectrum of immunoregulatory properties. They have been used in the treatment of a variety of inflammatory diseases; however, the therapeutic effects are still inconsistent owing to their heterogeneity. Spleen stromal cells have evolved to regulate the immune response at many levels as they are bathed in a complex inflammatory milieu during infection. Therefore, it is unknown whether they have stronge ...[more]

PMID: 36233119

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Project description:BackgroundThe intermediate filament protein nestin is used as a marker for neural stem cells, and its expression is inversely correlated with cellular differentiation. More recently, nestin expression has also been described in other cell types including multipotential mesenchymal stromal cells (MSCs). In this study, we examined the expression of nestin in equine, canine and human bone marrow-derived MSCs undergoing osteogenic differentiation, to determine whether nestin levels were attenuated as the cells acquired a more mature phenotype. In addition, the expression of nestin may be under the influence of cellular hypoxia, as nestin expression is known to increase in areas of ischemic tissue damage. Therefore, we also examined the effects of hypoxia on expression of nestin in human MSCs and examined a role for hypoxia inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in the response. Additionally, we quantified the temporal expression of nestin in the fracture callus during bone regeneration, a site that has been characterized as hypoxic.ResultsThere were no significant changes in nestin expression in MSCs during osteogenic differentiation. There was a significant increase in expression of nestin mRNA and protein in human MSCs in response to hypoxia (1% O2) or the chemical hypoxia mimetic desferroxamine. This may be due to upregulation of VEGF under hypoxia, as treatment of cells with the VEGF receptor antagonist CPO-P11 attenuated hypoxia-induced nestin expression. A significant increase in nestin mRNA expression was observed in the fracture callus of mice three and seven days post fracture.ConclusionsNestin was not a selective marker for MSCs, as its expression was maintained during osteogenic differentiation, in all species examined. Furthermore our data suggest that nestin expression can be induced by hypoxia, and that this increase in nestin is partially regulated by HIF-1α and VEGF. Interestingly, nestin levels were significantly upregulated at the fracture site. Further studies are required to understand the role of nestin in bone cell biology and ultimately bone regeneration.

Dataset Information

Nestin⁺ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function.

Publications

Nestin<sup>+</sup> Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function.

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Dataset Information

Nestin+ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function.

Publications

Nestin<sup>+</sup> Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Nestin⁺ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function.