title: Flexible Endoscopic Spray Application of Respiratory Epithelial Cells as Platform Technology to Apply Cells in Tubular Organs.
abstract: BACKGROUND
  Inoperable airway stenoses are currently treated by placing stents. A major problem of covered stents is missing mucociliary clearance, which is caused by covering the native respiratory epithelium. By coating a stent with respiratory epithelium, this problem can be overcome. However, no methods are available for efficient endoscopic cell seeding.
  
  
  METHODS
  We designed a flexible endoscopic spraying device based on a bronchoscope and tested it with respiratory epithelial cells. With this device cells can also be applied in a thin layer of fibrin glue. We evaluated the survival rate directly after spray application with a live-dead staining and the long-term differentiation capacity with histology and electron microscopy. Furthermore, the random distribution of cells when applied in a tube was analyzed and the macroscopic and microscopic characteristics of the endoscopic spray were investigated using high-speed visualization.
  
  
  RESULTS
  Spray visualization revealed a polydisperse character of the spray with the majority of droplets larger than epithelial cells. Spray application does not influence the survival rate and differentiation of respiratory epithelial cells. After 4 weeks, cells built up a pseudostratified epithelial layer with cilia and goblet cells. When cells are applied in a thin layer of fibrin gel into a tube, a nearest neighbor index of 1.2 is obtained, which suggests a random distribution of the cells.
  
  
  CONCLUSIONS
  This spraying device is a promising tool for application of various cell types onto stents or implants with high survival rates and homogeneous distribution as shown in this study for ovine respiratory epithelial cells. The system could also be used for cell therapy to locally apply cells to the diseased parts of hollow organs. For the first time, the fluid dynamics of a spray device for cells were examined to validate in vitro results.
authors.affiliation: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .
authors.forename: Anja Lena
authors.initials: AL
authors.lastname: Thiebes
authors.affiliation: 2 Institute of Heat and Mass Transfer, RWTH Aachen University , Aachen, Germany .
authors.forename: Manuel Armin
authors.initials: MA
authors.lastname: Reddemann
authors.affiliation: 2 Institute of Heat and Mass Transfer, RWTH Aachen University , Aachen, Germany .
authors.forename: Johannes
authors.initials: J
authors.lastname: Palmer
authors.affiliation: 2 Institute of Heat and Mass Transfer, RWTH Aachen University , Aachen, Germany .
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kneer
authors.affiliation: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .|3 Aachen-Maastricht Institute for Biobased Materials, Maastricht University at Chemelot Campus , Geleen, The Netherlands .
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhoevel
authors.affiliation: 1 Department of Tissue Engineering and Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University , Aachen, Germany .|4 Section for Pneumology, Department for Internal Medicine, RWTH Aachen University , Aachen, Germany .
authors.forename: Christian Gabriel
authors.initials: CG
authors.lastname: Cornelissen
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D004724:Endoscopy / Q000379:methods*; D004847:Epithelial Cells / Q000637:transplantation*; D011648:Pulmonary Adenomatosis, Ovine; D020545:Respiratory Mucosa / Q000637:transplantation*; D012756:Sheep; D014132:Trachea