Hypoxic preconditioning enhances mesenchymal stromal cell lung repair capacity

Idiopathic pulmonary fibrosis is a progressive, irreversible, debilitating, and fatal lung disease, characterized by parenchymal fibrosis with reduced lung volumes and respiratory failure. No lasting option for therapy is available other than transplantation. Mesenchymal stem/stromal cells home to sites of injury, decrease inflammation, have antifibrotic properties, and promote epithelial tissue repair, so their use has been suggested as potential therapy for idiopathic pulmonary fibrosis. Despite reported benefits, the amount of mesenchymal stromal cells engrafting to the lung decreases substantially soon after administration. New strategies, such as hypoxia preconditioning, have thus been investigated in an attempt to optimize the engraftment, survival, and paracrine properties of stem cells. Hypoxia induces the expression of prosurvival mediators, chemoattractants, and growth factors involved in cell proliferation, migration, angiogenesis, antioxidant, antiapoptotic, and antifibrotic properties in mesenchymal stromal cells, optimizing their lung repair capability in an animal model of idiopathic pulmonary fibrosis.