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Endoscopic atomization of mesenchymal stromal cells: in vitro study for local cell therapy of the lungs
Authors:Anja Lena Thiebes  Franziska E Uhl  Marie Hauser  Christian G Cornelissen  Stefan Jockenhoevel  Daniel J Weiss
Institution:1. Department of Biohybrid & Medical Textiles, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany;2. Vermont Lung Center, University of Vermont, Burlington, Vermont, USA;3. Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, Geleen, the Netherlands;4. Department of Experimental Medical Sciences, Lund University, Lund, Sweden;5. Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden;6. Clinic for Pneumology and Internistic Intensive Medicine (Medical Clinic V), University Hospital Aachen, Aachen, Germany
Abstract:Background aimsCell-based therapies of pulmonary diseases with mesenchymal stromal cells (MSCs) are increasingly under experimental investigation. In most of these, MSCs are administered intravenously or by direct intratracheal instillation. A parallel approach is to administer the cells into the lung by endoscopic atomization (spraying). In a previous study, the authors developed a flexible endoscopic atomization device that allows administration of respiratory epithelial cells in the lungs with high survival.MethodsIn this study, the authors evaluated the feasibility of spraying MSCs with two different endoscopic atomization devices (air and pressure atomization). Following atomization, cell viability was evaluated with live/dead staining. Subsequent effects on cytotoxicity, trilineage differentiation and expression of MSC-specific markers as well as on MSC metabolic activity and morphology were analyzed for up to 7 days.ResultsMSC viability immediately after spraying and subsequent metabolic activity for 7 days was not influenced by either of the devices. Slightly higher cytotoxicity rates could be observed for pressure-atomized compared with control and air-atomized MSCs over 7 days. Flow cytometry revealed no changes in characteristic MSC cell surface marker expression, and morphology remained unchanged. Standard differentiation into osteocytes, chondrocytes and adipocytes was inducible after atomization.ConclusionsIn the literature, a minimal survival of 50% was previously defined as the cutoff value for successful cell atomization. This is easily met with both of the authors’ devices, with more than 90% survival. Thus, there is a potential role for atomization in intrapulmonary MSC-based cell therapies, as it is a feasible and easily utilizable approach based on clinically available equipment.
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