Article ; Online: GVHD-derived plasma as a priming strategy of mesenchymal stem cells.
2020 Volume 11, Issue 1, Page(s) 156
Abstract: Background: Mesenchymal stem cell (MSC) therapy is an important alternative for GVHD treatment, but a third of patients fail to respond to such therapy. Therefore, strategies to enhance the immunosuppressive potential of MSCs constitute an active area ... ...
| Abstract | Background: Mesenchymal stem cell (MSC) therapy is an important alternative for GVHD treatment, but a third of patients fail to respond to such therapy. Therefore, strategies to enhance the immunosuppressive potential of MSCs constitute an active area of investigation. Here, we proposed an innovative priming strategy based on the plasma obtained from GVHD patients and tested whether this approach could enhance the immunosuppressive capacity of MSCs. Methods: We obtained the plasma from healthy as well as acute (aGVHD) and chronic (cGVHD) GVHD donors. Plasma samples were characterized according to the TNF-α, IFN-γ, IL-10, IL-1β, IL-12p40, and IL-15 cytokine levels. The MSCs primed with such plasmas were investigated according to surface markers, morphology, proliferation, mRNA expression, and the capacity to control T cell proliferation and Treg generation. Results: Interestingly, 57% of aGVHD and 33% of cGVHD plasmas significantly enhanced the immunosuppressive potential of MSCs. The most suppressive MSCs presented altered morphology, and those primed with cGHVD displayed a pronounced overexpression of ICAM-1 on their surface. Furthermore, we observed that the ratio of IFN-γ to IL-10 cytokine levels in the plasma used for MSC priming was significantly correlated with higher suppressive potential and Treg generation induction by primed MSCs, regardless of the clinical status of the donor. Conclusions: This work constitutes an important proof of concept which demonstrates that it is possible to prime MSCs with biological material and also that the cytokine levels in the plasma may affect the MSC immunosuppressive potential, serving as the basis for the development of new therapeutic approaches for the treatment of immune diseases. |
|---|---|
| MeSH term(s) | Cytokines ; Graft vs Host Disease ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; T-Lymphocytes, Regulatory ; Tumor Necrosis Factor-alpha |
| Chemical Substances | Cytokines ; Tumor Necrosis Factor-alpha |
| Language | English |
| Publishing date | 2020-04-16 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2548671-8 |
| ISSN | 1757-6512 ; 1757-6512 |
| ISSN (online) | 1757-6512 |
| ISSN | 1757-6512 |
| DOI | 10.1186/s13287-020-01659-x |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.