GVHD-derived plasma as a priming strategy of mesenchymal stem cells
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 innovat...
| Main Authors: | Carvalho, Amandda Évelin Silva, Rodrigues, Leane Perim, Schiavinato, Josiane Lilian, Alborghetti, Marcos Rodrigo, Bettarello, Gustavo, Simões, Belinda Pinto, Neves, Francisco de Assis Rocha, Panepucci, Rodrigo Alexandre, Carvalho, Juliana Lott de, Araujo, Felipe Saldanha de |
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| Format: | Artigo |
| Language: | Inglês |
| Published: |
BMC
2020
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| Subjects: | |
| Online Access: |
https://repositorio.unb.br/handle/10482/39539 https://doi.org/10.1186/s13287-020-01659-x |
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| Summary: |
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. |
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