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- W4313366431 abstract "Abstract Total body irradiation is often used as a conditioning regimen for bone marrow transplants but can cause life threatening damage to host tissues especially the bone marrow. Developing a cellular therapy that can protect the bone marrow from acute radiation syndrome and stimulate hematopoiesis is a priority for patients exposed to therapeutic or even accidental radiation injury. In this study, exosomes derived from MSCs stimulated with the TLR4 agonist lipopolysaccharide (LPS) were used to alternatively activate human monocytes, termed LPS EEMos, as a potential novel radioprotective cellular therapy. LPS EEMos expressed higher levels of PD-L1 (p<0.0001), and lower levels of CD16 (p<0.01), CD86 (p<0.01), and CD206 (p<0.0001) by flow cytometry compared to monocytes educated with exosomes from unstimulated MSCs (EEMos). Using qPCR, increased gene expression in LPS EEMos of IL-10 (p<0.05), IDO (p<0.001), FGF2 (p<0.05), IL-15 (p<0.05), and IL-6 (p<0.0001) were detected compared to EEMos. Using a xenogeneic radiation injury model, infusion of human LPS EEMos 4 hours after lethal radiation led to reduced clinical scores and an increased survival at 40 days post-infusion, as compared to infusions of PBS, EEMos, and monocytes alone, all of which led to worse clinical scores and 0% survival with uniform death by 20 days (p<0.05). Complete blood cell counts in LPS EEMo recipients showed leukocyte, erythrocyte and platelet counts equivalent to non-irradiated mice, demonstrating complete restoration of hematopoiesis. Infusion of LPS EEMos may be a useful strategy to protect the bone marrow from acute radiation syndrome by expression of anti-inflammatory molecules and cytokines that promote hematopoiesis/engraftment." @default.
- W4313366431 created "2023-01-06" @default.
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- W4313366431 date "2019-05-01" @default.
- W4313366431 modified "2023-09-26" @default.
- W4313366431 title "Human monocytes educated with exosomes from TLR4 primed mesenchymal stem cells treat acute radiation syndrome by promoting hematopoietic recovery" @default.
- W4313366431 doi "https://doi.org/10.4049/jimmunol.202.supp.69.39" @default.
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