Pretreatment with bone marrow-derived mesenchymal stromal cell-conditioned media confers pulmonary ischemic tolerance

Objective: Mesenchymal stromal cell-based therapies have demonstrated efficacy in treating a variety of diseases. Despite the potential benefits, there are still significant hurdles that need to be overcome for clinical use. We describe a cell-free-based immunotherapy approach for inducing pulmonary ischemic tolerance by using mesenchymal stromal cell-conditioned media. Methods: In our well-established lung ischemia-reperfusion model, we pretreated with mesenchymal stromal cell-conditioned media 30 minutes before injury. To determine the degree of lung injury, we assessed for changes in lung vascular permeability, proinflammatory cytokines and cellular infiltrates in bronchoalveolar lavage, and histopathology. Macrophage and T-cell subsets were assessed by immunohistochemistry. Results: Pretreatment with mesenchymal stromal cell-conditioned media conferred protection against lung ischemia-reperfusion injury. This protection is characterized by a significant reduction in proinflammatory cytokines, a decrease in infiltrating inflammatory cells, and increases in M2-like macrophages and regulatory T cells. Conclusions: Cell-free mesenchymal stromal cell-conditioned media therapy confers pulmonary ischemic tolerance. This therapy uses paracrine factors that provide beneficial protective effects by immunomodulating the inflammatory response in resident and infiltrating cell subsets.