Intravenous administration of human umbilical cord mesenchymal stromal cells leads to an inflammatory response in the lung

Abstract

Mesenchymal stromal cells (MSCs) administered intravenously (IV) have shown efficacy in pre-clinical models of various diseases. This is despite the cells not reaching the site of injury due to entrapment in the lungs. The ability of MSCs to modulate immune responses has been proposed as one of the mechanisms by which these cells provide therapeutic benefits, irrespective of whether they are sourced from bone marrow, adipose tissue or umbilical cord. To better understand how MSCs affect innate immune cell populations in the lung, we evaluated the percentage, distribution and phenotype of neutrophils, monocytes and macrophages by flow cytometry and histological analyses after delivering human umbilical cord-derived MSCs (hUC-MSCs) IV into immunocompetent mice. After 2 h, we observed a sharp increase in neutrophils, and pro-inflammatory monocytes and macrophages. Moreover, these immune cells localised in the vicinity of the MSCs suggesting an active role in their clearance. By 24 h, we detected an increase in anti-inflammatory monocytes and macrophages. These results suggest that the IV injection of hUC-MSCs leads to an initial inflammatory phase in the lung shortly after injection, followed by a resolution phase 24 h later.