title: Atomized Human Amniotic Mesenchymal Stromal Cells for Direct Delivery to the Airway for Treatment of Lung Injury.
abstract: Current treatment regimens for inhalation injury are mainly supportive and rely on self-regeneration processes for recovery. Cell therapy with mesenchymal stromal cells (MSCs) is increasingly being investigated for the treatment of inhalation injury. Human amniotic MSCs (hAMSCs) were used in this study due to their potential use in inflammatory and fibrotic conditions of the lung. This study aimed at demonstrating that hAMSCs can be atomized with high viability, for the purpose of achieving a more uniform distribution of cells throughout the lung. Another aim of this study was to set ground for future application to healthy and diseased lungs by demonstrating that hAMSCs were able to survive after being sprayed onto substrates with different stiffness.
  
  
  
  Two methods of atomization were evaluated, and the LMA MAD780 device was selected for atomizing hAMSCs for optimized delivery. To mimic the stiffness of healthy and diseased lungs, gelatin gel (10% w/v) and tissue culture plastic were used as preliminary models. Poly-l-lysine (PLL) and collagen I coatings were used as substrates on which the hAMSCs were cultured after being sprayed.
  
  
  
  The feasibility of atomizing hAMSCs was demonstrated with high cell viability (81 ± 3.1% and 79 ± 11.6% for cells sprayed onto plastic and gelatin, respectively, compared with 85 ± 4.8% for control/nonsprayed cells) that was unaffected by the different stiffness of substrates. The presence of the collagen I coating on which the sprayed cells were cultured yielded higher cell proliferation compared with both PLL and no coating. The morphology of sprayed cells was minimally compromised in the presence of the collagen I coating.
  
  
  
  This study demonstrated that hAMSCs are able to survive after being sprayed onto substrates with different stiffness, especially in the presence of collagen I. Further studies may advance the effectiveness of cell therapy for lung regeneration.
authors.affiliation: 1 Faculty of Pharmacy, The University of Sydney , Sydney, Australia .
authors.forename: Sally Yunsun
authors.initials: SY
authors.lastname: Kim
authors.affiliation: 2 Department Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .|3 Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, The University of Sydney , Sydney, Australia .|4 Discipline of Pharmacology, The University of Sydney , Sydney, Australia .
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.affiliation: 5 ANZAC Research Institute, The University of Sydney , Concord, Australia .
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 6 Australian Centre for Microscopy & Microanalysis, The University of Sydney , Sydney, Australia .
authors.forename: Eleanor P W
authors.initials: EP
authors.lastname: Kable
authors.affiliation: 7 College of Medicine, University of Vermont College of Medicine , Burlington, Vermont.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.affiliation: 1 Faculty of Pharmacy, The University of Sydney , Sydney, Australia .
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.affiliation: 1 Faculty of Pharmacy, The University of Sydney , Sydney, Australia .|8 Australian Institute of Nanoscale Science and Technology, The University of Sydney , Sydney, NSW 2006, Australia .
authors.forename: Wojciech
authors.initials: W
authors.lastname: Chrzanowski
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000653:Amniotic Fluid / Q000166:cytology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry; D004867:Equipment Design; D005240:Feasibility Studies; D005780:Gelatin / Q000737:chemistry; D005782:Gels; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D009330:Nebulizers and Vaporizers; D011107:Polylysine / Q000737:chemistry; D012038:Regeneration; D013997:Time Factors
chemical_list: D000336:Aerosols; D024042:Collagen Type I; D005782:Gels; D011107:Polylysine; D005780:Gelatin
keywords: atomic force microscopy; cell atomization; cell delivery; collagen; mesenchymal stromal cells; pulmonary delivery