Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy

Authors

Ioannis Koutroulis, Department of Pediatrics, Division of Emergency Medicine, Children's National Hospital, Washington, DC 20010, USA.
Panagiotis Kratimenos, George Washington University School of Medicine and Health Sciences, Washington, DC 20010, USA.
Claire Hoptay, Children's National Research Institute, Washington, DC 20010, USA.
Wade N. O'Brien, Dartmouth College Geisel School of Medicine, Hanover, NH 03755, USA.
Georgios Sanidas, Children's National Research Institute, Washington, DC 20010, USA.
Chad Byrd, Children's National Research Institute, Washington, DC 20010, USA.
Maria Triantafyllou, Children's National Research Institute, Washington, DC 20010, USA.
Evan Goldstein, Augusta University Medical College of Georgia, Augusta, GA 30912, USA.
Beata Jablonska, Children's National Research Institute, Washington, DC 20010, USA.
Manish Bharadwaj, Agilent Inc, Santa Clara, CA 95051, USA.
Vittorio Gallo, George Washington University School of Medicine and Health Sciences, Washington, DC 20010, USA.
Robert Freishtat, Department of Pediatrics, Division of Emergency Medicine, Children's National Hospital, Washington, DC 20010, USA.

Document Type

Journal Article

Publication Date

8-16-2024

Journal

iScience

Volume

27

Issue

8

DOI

10.1016/j.isci.2024.110573

Keywords

Biological sciences; Immune system disorder; Immunology

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that results in high mortality and long-term sequela. The central nervous system (CNS) is susceptible to injury from infectious processes, which can lead to clinical symptoms of septic encephalopathy (SE). SE is linked to a profound energetic deficit associated with immune dysregulation. Here, we show that intravenous administration of adipose tissue mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) in septic mice improved disease outcomes by reducing SE clinical severity, restoring aerobic metabolism, and lowering pro-inflammatory cytokines in the cerebellum, a key region affected by SE. Our high throughput analysis showed that MSC-derived sEVs partially reversed sepsis-induced transcriptomic changes, highlighting the potential association of miRNA regulators in the cerebellum of MSC-derived sEV-treated mice with miRNAs identified in sEV cargo. MSC-derived sEVs could serve as a promising therapeutic agent in SE through their favorable immunometabolic properties.

APA Citation

Koutroulis, Ioannis; Kratimenos, Panagiotis; Hoptay, Claire; O'Brien, Wade N.; Sanidas, Georgios; Byrd, Chad; Triantafyllou, Maria; Goldstein, Evan; Jablonska, Beata; Bharadwaj, Manish; Gallo, Vittorio; and Freishtat, Robert, "Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy" (2024). GW Authored Works. Paper 5472.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5472

Department

Pediatrics