Exosome educated macrophages – a potential effective cellular therapy for the management of acute radiation syndrome

exosomes

In the setting of radiation-induced trauma, exposure to high levels of radiation can cause an acute radiation syndrome (ARS) causing bone marrow (BM) failure, leading to life threatening infections, anemia and thrombocytopenia. Researchers from the University of Wisconsin School of Medicine and Public Health have previously shown that human macrophages educated with human mesenchymal stem cells (MSCs) by co-culture can significantly enhance survival of mice exposed to lethal irradiation. In this study, they investigated whether exosomes isolated from MSCs could replace direct co-culture with MSCs to generate exosome educated macrophages (EEMs). Functionally unique phenotypes were observed by educating macrophages with exosomes from MSC’s (EEMs) primed with bacterial lipopolysaccharide (LPS) at different concentrations (LPS-low EEMs or LPS-high EEMs). LPS-high EEMs were significantly more effective than uneducated macrophages, MSCs, EEMs, or LPS-low EEMs in extending survival after lethal ARS in vivo. Moreover, LPS-high EEMs significantly reduced clinical signs of radiation injury and restored hematopoietic tissue in the BM and spleen as determined by complete blood counts and histology. LPS-high EEMs showed significant increases in gene expression of STAT3, secretion of cytokines like IL-10 and IL-15 and production of growth factors like FLT-3L. LPS-EEMs also showed increased phagocytic activity, which may aid with tissue remodeling. LPS-high EEMs have the potential to be an effective cellular therapy for the management of ARS.

Kink JA et al. (2019) Macrophages Educated with Exosomes from Primed Mesenchymal Stem Cells Treat Acute Radiation Syndrome by Promoting Hematopoietic Recovery. Biology of Blood and Marrow Transplantation [Epub ahead of print]. [abstract]

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