title: Recellularization of decellularized lung scaffolds is enhanced by dynamic suspension culture.
abstract: Strategies are needed to improve repopulation of decellularized lung scaffolds with stromal and functional epithelial cells. We demonstrate that decellularized mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor, termed the rotating wall vessel (RWV), contained more cells with decreased apoptosis, increased proliferation and enhanced levels of total RNA compared to static recellularization conditions. These results were observed with two relevant mouse cell types: bone marrow-derived mesenchymal stromal (stem) cells (MSCs) and alveolar type II cells (C10). In addition, MSCs cultured in decellularized lungs under static but not bioreactor conditions formed multilayered aggregates. Gene expression and immunohistochemical analyses suggested differentiation of MSCs into collagen I-producing fibroblast-like cells in the bioreactor, indicating enhanced potential for remodeling of the decellularized scaffold matrix. In conclusion, dynamic suspension culture is promising for enhancing repopulation of decellularized lungs, and could contribute to remodeling the extracellular matrix of the scaffolds with subsequent effects on differentiation and functionality of inoculated cells.
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Crabbé
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Shameema F
authors.initials: SF
authors.lastname: Sarker
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Bonenfant
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barrila
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Borg
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America; School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Nickerson
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology; D000818:Animals; D017209:Apoptosis; D061249:Batch Cell Culture Techniques; D019149:Bioreactors; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D008168:Lung / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D023421:Models, Animal; D012038:Regeneration; D054457:Tissue Scaffolds