Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 25, Issue 11, Pages 2124-2133Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2019.07.026
Keywords
Mesenchymal stem cells; Radiation injury; Exosomes; Macrophages; Acute radiation syndrome; Hematopoiesis
Categories
Funding
- University of Wisconsin Carbone Cancer Center (UWCCC) Flow Cytometry and Experimental Pathology (National Institutes of Health) [P30 CA014520]
- Crystal Carney Fund for Leukemia Research [SU2C-AACR-DT-27-17]
- NIH/National Center for Advancing Translational Sciences [UL1TR000427]
- NIH/NCI [P30 CA014520, K08 CA174750]
- Stand Up To Cancer is a division of the Entertainment Industry Foundation
- scientific partner of SU2C
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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. We have previously shown that human macrophages educated with human mesenchymal stem cells (MSCs) by coculture can significantly enhance survival of mice exposed to lethal irradiation. In this study, we investigated whether exosomes isolated from MSCs could replace direct coculture with MSCs to generate exosome educated macrophages (EEMs). Functionally unique phenotypes were observed by educating macrophages with exosomes from MSCs (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. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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