Macrophages Educated with Exosomes from Primed Mesenchymal Stem Cells Treat Acute Radiation Syndrome by Promoting Hematopoietic Recovery. Biol Blood Marrow Transplant 2019 Nov;25(11):2124-2133
Date
08/09/2019Pubmed ID
31394269Pubmed Central ID
PMC6861683DOI
10.1016/j.bbmt.2019.07.026Scopus ID
2-s2.0-85072691542 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
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.
Author List
Kink JA, Forsberg MH, Reshetylo S, Besharat S, Childs CJ, Pederson JD, Gendron-Fitzpatrick A, Graham M, Bates PD, Schmuck EG, Raval A, Hematti P, Capitini CMAuthor
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acute Radiation SyndromeAnimals
Exosomes
Female
Hematopoiesis
Humans
Lipopolysaccharides
Macrophages
Male
Mice
Mice, Inbred NOD
Radiation Injuries, Experimental
