Macrophages Educated with Exosomes from Primed Mesenchymal Stem Cells Treat Acute Radiation Syndrome by Promoting Hematopoietic Recovery.

Autor: Kink JA; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Forsberg MH; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Reshetylo S; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Besharat S; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Childs CJ; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Pederson JD; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Gendron-Fitzpatrick A; The Comparative Pathology Laboratory, Research Animal Resource Center, University of Wisconsin, Madison, Wisconsin., Graham M; The Comparative Pathology Laboratory, Research Animal Resource Center, University of Wisconsin, Madison, Wisconsin., Bates PD; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Schmuck EG; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Raval A; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Hematti P; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin., Capitini CM; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin. Electronic address: ccapitini@pediatrics.wisc.edu.
Jazyk: angličtina
Zdroj: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2019 Nov; Vol. 25 (11), pp. 2124-2133. Date of Electronic Publication: 2019 Aug 05.
DOI: 10.1016/j.bbmt.2019.07.026
Abstrakt: 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.
(Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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