Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severeE. colipneumonia

Abstract

In summary, MSC MVs increased alveolar fluid clearance and reduced lung protein permeability, and pretreatment with Poly (I:C) enhanced the antimicrobial activity of MVs in an ex vivo perfused human lung with severe bacteria pneumonia.

Extracellular Vesicles in ARDS: New Insights into Pathogenesis with Novel Clinical Applications

“…These findings explain the ability of mesenchymal stromal cell extracellular vesicles to restore alveolar fluid clearance in ex vivo human lungs [41]. In an E. coli pneumonia model using ex vivo human lungs, administration of mesenchymal stromal cell extracellular vesicles reduced bacterial load within the alveolar space, reduced protein permeability, and increased alveolar fluid clearance [42]. Mouse studies indicated that mesenchymal stromal cell extracellular vesicle transfer of miR-145 to macrophages was responsible for the increased bacterial phagocytosis [43].…”

Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

“…In a mouse model of lung injury, Bhattacharya's group showed that bone marrow-derived MSCs transfer red mitochondrial DNA to host alveolar cells restoring their bioenergetics and surfactant secretion, while reducing mortality (Islam et al, 2012). Administration of MSC microvesicles in lungs on EVLP led to improved alveolar fluid clearance and reduced bacterial load in human lungs with E. coli pneumonia (Park et al, 2019), and decreased weight gain and improved airway and hemodynamic parameters in human lungs rejected for transplantation (Gennai et al, 2015).…”

Where next for cell-based therapy in ARDS

“…This mechanism helps explain why alveolar macrophages are required for the antimicrobial effects of MSCs 22. In this issue of Thorax , the findings from a human ex vivo model investigating intravenous MSC-derived MVs as a therapy for E. coli pneumonia are reported by Park et al 7. Their findings include that MVs improved AFC, decreased lung protein permeability and were associated with a reduced alveolar neutrophil count.…”

“…In the latest development towards a cell-based therapy for ARDS, Park et al  report the use of an human ex vivo lung perfusion model of ARDS to investigate MSC-derived microvesicles (MVs) as a therapy for ARDS 7. MSCs are pluripotent cells that can be extracted from various sources including bone marrow, adipose tissue and umbilical cord.…”