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Matthew Forsberg, Postdoctoral Fellow, Pediatrics (Capitini lab), “Monocytes educated with exosomes from TLR-4 primed mesenchymal stem cells treat acute radiation syndrome by promoting hematopoietic recovery”
February 12 @ 12:00 pm - 1:00 pm
Topic: Monocytes educated with exosomes from TLR-4 primed mesenchymal stem cells treat acute radiation syndrome by promoting hematopoietic recovery
Abstract: Developing a cellular therapy that can protect the bone marrow is a priority for patients exposed to accidental or intentional radiation injury. Many groups have studied mesenchymal stem cells (MSCs) as a radioprotective cell therapy, but these cells have not yet shown benefit in the clinic. We hypothesize that alternatively activated human monocytes are superior to MSCs against lethal radiation injury. In this study, we generated radioprotective human monocytes by educating them with exosomes derived from MSCs stimulated with the TLR4 agonist lipopolysaccharide (LPS), termed LPS EEMos. We found that 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 derived from unstimulated MSCs (EEMos). Using qPCR, we detected 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) compared to EEMos. Using a xenograft mouse model, infusion of human LPS EEMos 4 hours after lethal radiation injury led to an increased survival rate at 40 days post-infusion, as compared to infusions of PBS, EEMos, and monocytes alone, all of which led to 0% survival with uniform death by 20 days. Complete blood cell counts in LPS EEMo recipients show leukocyte, erythrocyte and platelet counts equivalent to non-irradiated mice. We conclude that LPS EEMos may be a useful cell subset to protect the bone marrow against radiation injury by expression of anti-inflammatory molecules and augmentation of host hematopoiesis