Mesenchymal stromal cell tratment for COPD : experimental and clinical studies

Abstract

The studies described in

this thesis have provided novel insight into airway epithelial repair

mechanisms and their modulation by cigarette smoke, and insight into

mesenchymal stromal cell treatment of COPD. We have shown that cigarette smoke delays wound repair in injured airway epithelial cells and that the inflammatory mediators present in the lungs of patients with COPD increase the regenerative potential of MSCs. We have furthermore demonstrated that MSCs from patients with severe COPD can be safely used as a cell-based therapy to treat these patients. Many questions remain regarding route of administration, dosage and timing of MSCs administration in COPD. Useful outcome parameters to assess MSC-mediated effects on lung tissue are largely undetermined, and we propose to include analysis of effects on endothelial and inflammatory cells in future clinical trials. The use of ALI-PBEC and alveolar epithelial cell cultures and ex vivo lung perfusion models will help to advance our understanding of the potential of MSCs in pulmonarydiseases. Parallel developments in other areas of regenerative medicine, including those related to induced pluripotent stem cells and ex vivo organ engineering, will synergistically advance the much awaited therapeutic arsenal that is needed to restore pulmonary function in COPD