EXPERIMENTAL AND CLINICAL AIRWAY RESTORATION BY MESENCHYMAL STROMAL CELLS AUTOLOGOUS ENDOSCOPIC TRANSPLANTATION

Post resectional broncho-pleural fistula is a pathological connection between the airways and the pleural space that may develop after lung resection. It may be caused by incomplete bronchial closure, impediment of bronchial stump wound healing, or stump destruction by residual neoplastic tissue; its mortality ranges from 12.5 to 71.2%, therefore it is still the most feared complication after curative lung resection; for this reason the healing effects promoted by stem cells - by transformation into mature cells with a specialized function or by enhancing intrinsic repair mechanisms -may represent an effective and only partially explored therapeutic option . Mesenchymal stromal cells have the ability to migrate and engraft at sites of inflammation and injury in response to cytokines, chemokines, and growth factors at a wound site and they can exert local reparative effects through transdifferentiation into tissue-specific cell types or via the paracrine secretion of soluble factors with anti-inflammatory and wound-healing activities. We proposed, on an animal model, an autologous bone marrow derived mesenchymal stromal cells transplantation: it allowed bronchial stump healing by extraluminal fibroblast proliferation and collagenous matrix development. Encouraged by experimental bronchial wall restoration in large animals and by functional human organ replacement elsewhere, we undertook autologous bone marrow derived mesenchymal stromal cells bronchoscopic transplantation to treat a patient who developed broncho-pleural fistula. The bronchoscopic transplantation of bone marrow-derived mesenchymal stromal cells in our patient appeared to help close this small-caliber post resectional broncho-pleural fistula, further boosting regenerative medicine approach for airway diseases. Considering the need to specifically track mesenchymal stromal cells following transplantation in order to evaluate different method of implantation, to follow their migration within the body and to quantify their accumulation at the target, we proposed magnetic resonance imaging tracking both by superparamagnetic 6 iron oxide particles and perfluorocarbon nanoemulsion formulations , demonstrating that were both effective, without altering cell viability or differentiation. Finally we proposed adipose derived mesenchymal stromal cells bronchoscopic transplantation and intra venous injection of Granulocite Colony Stimulating Factors as a faster method and a new frontier in airway restoration.