1. Modulating endothelial cells with EGFL7 to diminish aGVHD after allogeneic bone marrow transplantation in mice
- Author
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Francis Daudelin, Parvathi Ranganathan, Charles-Etienne Bigras, Moutuaata M. Moutuou, Sonu Kaylan, Alex Ruddich, Eric Naumann, Adrienne M. Dorrance, Marie Goulard, Ramiro Garzon, Martin Guimond, Nathalie Sell, Malith Karunasiri, Rohan Sudhir Kulkarni, Chinmayee Goda, Antoire Ackaoui, and Sofia Kovovich
- Subjects
Allogeneic transplantation ,Immunology ,Graft vs Host Disease ,Inflammation ,Biochemistry ,Mice ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Animals ,Transplantation, Homologous ,Cause of death ,Bone Marrow Transplantation ,integumentary system ,Marrow transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Endothelial Cells ,Cell Biology ,Hematology ,Endothelial stem cell ,surgical procedures, operative ,T cell migration ,EGFL7 ,Stem cell ,medicine.symptom ,business - Abstract
Acute graft versus host (aGVHD) is the second cause of death after allogeneic-hematopoietic stem cell transplant (allo-HSCT) underscoring the need for novel therapies. Based on previous work that endothelial cell dysfunction is present in aGVHD and that epidermal growth factor-like domain 7 (EGFL7) plays a significant role in decreasing inflammation by repressing endothelial cell activation and T cell migration, we hypothesized that increasing EGFL7 levels after allo-HSCT will diminish the severity of aGVHD. Here, we show that treatment with recombinant EGFL7 (rEGFL7) decreases aGVHD severity and improves survival in recipient mice after allogeneic transplantation with respect to controls without affecting graft versus leukemia effect. Histopathology analysis revealed higher amount of leukocyte infiltration in both large intestine and liver of PBS group compared to rEGFL7-treated mice. Furthermore, damage to the gut was reduced in EGFL7 treated mice. Finally, we showed that rEGFL7 treatment results in higher thymocytes, T, B and dendritic cells in recipient mice after allo-HSCT. This study constitutes a proof of concept of the ability of rEGFL7 therapy to reduce GHVD severity and mortality after allo-HSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
- Published
- 2021