Abstract
Sepsis accounts for 1 in 5 deaths worldwide, making it a prominent societal, economic, and therapeutic burden. Sepsis progression is categorised into three phases, early, transitionary, and late. Since 70% of all sepsis related deaths occur in the late phase we are targeting the transitionary phase to restore immune homeostasis. Mesenchymal stromal cells (MSC) were used as they exhibit potent immunomodulatory properties and we have previously shown efficacy in an early phase E. coli model of pneumonia.
The MSCs used in this study were naïve, cytomix licenced (TNF-α, IL-1β, and IFN-γ), and hypoxia cultured. They were administered via tail vein cannula to our rodent animal model 1 hour after the intracheal bolus of K. pneumoniae. After 3 days physiological parameters, bronchoalveolar lavage fluid (BALF), and immune cell profiles were assessed.
Cytomix licensed MSCs provided a protective role in the airspace by significantly reducing colony forming units of K. pneumoniae (A), improved the survival of BALF cells minus granulocytes (other cells) (B), increased the proportion of CD4+ to CD8+ T-cells (C), enhanced the phagocytic capabilities of alveolar macrophages in the absence and presence of an ex vivo endotoxin injury (D), and restored the number of neutrophils to near sham levels (E). Licensing of MSCs improved their therapeutic efficacy and restored immune homeostasis.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 85.
This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.
This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022