ORCID Profile
0000-0001-8964-319X
Current Organisations
University of Rome Tor Vergata
,
First Affiliated Hospital of Soochow University
,
Soochow University
,
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
,
Member of The Academy of Europe
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Publisher: Springer Science and Business Media LLC
Date: 23-01-2018
Publisher: Wiley
Date: 02-05-2021
Abstract: Mesenchymal stromal cells (MSCs) function as a formidable regulator of inflammation and tissue homeostasis and expanded MSCs are shown to be effective in treating various inflammatory diseases. Their therapeutic effects require the existence of certain inflammatory cytokines. However, in the absence of sufficient proinflammatory stimuli or in the presence of anti‐inflammatory medications, MSCs are animated to promote immune responses and unable to alleviate inflammatory disorders. In this study, it is demonstrated that steroid co‐administration interferes the efficacy of MSCs in treating acute graft‐versus‐host disease (aGvHD). Molecular analysis reveals that vascular endothelial growth factor C (VEGF‐C) is highly induced in MSCs by steroids and TNF α and VEGF‐C in turn promotes CD8 + T cell response. This immune promoting effect is abolished by blockade or specific genetic ablation of VEGFR3 in CD8 + T cells. Additionally, administration of VEGF‐C alone exacerbates aGvHD progression through eliciting more vigorous CD8 + T cell activation and proliferation. Further studies demonstrate that VEGF‐C augments the PI3K/AKT signaling process and the expression of downstream genes, such as Cyclin D1. Thus, the data demonstrate that steroids can reverse the immunosuppressive effect of MSCs via promoting VEGF‐C‐augmented CD8 + T cell response and provide novel information for designing efficacious MSC‐based therapies.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2019
DOI: 10.1038/S41419-019-1583-4
Abstract: Mesenchymal stem cells (MSCs) are a population of multipotent cells with a superior ability to promote tissue repair by regulating regeneration and inflammation. Effective application of MSCs in disease treatment relies on the production of relatively homogeneous cell population. However, the cellular heterogeneity and the differentiation trajectories of in vitro expanded MSCs remain largely unclear. We profiled the transcriptomes of 361 single MSCs derived from two umbilical cords (UC-MSCs). These UC-MSCs were harvested at different passages and stimulated with or without inflammatory cytokines. Weighted gene correlation network analysis revealed that UC-MSCs surprisingly possess only limited heterogeneity, regardless of donors, and passages. We also found that upon pretreatment with inflammatory cytokines (IFNγ and TNFα), a classical strategy that can improve the efficiency of MSC-based therapy, MSCs exhibited uniformed changes in gene expression. Cell cycle-based principal component analysis showed that the limited heterogeneity identified in these UC-MSCs was strongly associated with their entrance into the G2/M phase. This was further proven by the observation that one featured gene, CD168, was expressed in a cell cycle-dependent manner. When CD168 high UC-MSCs were sorted and cultured in vitro, they again showed similar CD168 expression patterns. Our results demonstrated that in vitro expanded UC-MSCs are a well-organized population with limited heterogeneity dominated by cell cycle status. Thus, our studies provided information for standardization of MSCs for disease treatment.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2023
Location: No location found
Location: China
No related grants have been discovered for Yufang Shi.