Duration of Acute Graft versus Host Disease prevention caused by inhibition of T-cells by Interferon Gamma Mesenchymal Stromal Cells Open Access
Foster, William (Spring 2024)
Abstract
Hematopoietic cell transplantation as a treatment for hematological diseases has the potential of causing acute graft versus host disease (GVHD) in patients. GVHD is caused by the T-cells of the graft attacking the host’s tissue. Unfortunately, there are few drugs that have been proven to treat GVHD, but recent research into mesenchymal stromal cells has shown promise for a new form of treatment. When MSCs are primed with interferon-gamma, they can inhibit the proliferation of alloreactive T-cells. Using these γMSCs, the onset of GVHD can be delayed by inhibiting donor T-cell proliferation for a limited time in our model. We aim to find the duration of GVHD prevention caused by γMSCs and looking into where the T-cells migrate after recovery from γMSC suppression. Without treatment, mice were shown to develop GVHD in about 6 to 8 days after transplant. The γMSCs were shown to delay the onset of GVHD for about 11 to 16 days, with the mice developing GVHD after about 17 to 24. After the effect of γMSCs has waned, GVHD begins to progress like that of the untreated group. It was also found that the T-cells migrate primarily to the secondary lymphoid organs, with the predominant form of T-cells present being effector memory T-cells in the untreated group and central memory T-cells in the group treated with γMSC. The γMSCs seem to influence the differentiation of T-cells into central memory T-cells rather than effector memory T-cells, preventing tissue damage and thus the progression of GVHD. This data gives more insight into the still unknown mechanism of γMSCs inhibition of T-cells. With a better understanding of the duration of γMSCs, research into using repeat doses of γMSCs to further prolong the delay of GVHD can be conducted, opening the potential for a new preventive treatment of GVHD using γMSCs.
Table of Contents
Table of Contents
Introduction________________________1
Results______________________________3
Discussion_________________________10
Methods___________________________12
Table of Figures___________________14
References_________________________22
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