title: Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung.
abstract: This study summarizes the development and testing of a scaffold to promote engraftment of cells in the distal lung. A fibrinogen-fibronectin-vitronectin hydrogel (FFVH) was developed and optimized with respect to its mechanical and biological properties for this application. In vitro, FFVH scaffolds promoted attachment, histiotypic growth and expression of basement membrane proteins by primary ovine lung mesenchymal cells derived from lung biopsies. In vivo testing was then performed to assess the ability of FFVHs to promote cell engraftment in the sheep lung. Treatment with autologous cells delivered using FFVH was clinically well tolerated. Cells labelled with a fluorescent dye (PKH-26) were detected at treatment sites after 1 month. Tissue mass (assessed by CT imaging) and lung perfusion (assessed by nuclear scintigraphy) were increased at emphysema test sites. Post-treatment histology demonstrated cell proliferation and increased elastin expression without scarring or collapse. No treatment-related pathology was observed at healthy control sites. FFVH scaffolds promote cell attachment, spreading and extracellular matrix expression in vitro and apparent engraftment in vivo, with evidence of trophic effects on the surrounding tissue. Scaffolds of this type may contribute to the development of cell-based therapies for patients with end-stage pulmonary diseases.
authors.affiliation: Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. eingenito@partners.org
authors.forename: Edward P
authors.initials: EP
authors.lastname: Ingenito
authors.forename: Elif
authors.initials: E
authors.lastname: Sen
authors.forename: Larry W
authors.initials: LW
authors.lastname: Tsai
authors.forename: Shankar
authors.initials: S
authors.lastname: Murthy
authors.forename: Andrew
authors.initials: A
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005340:Fibrinogen / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D005434:Flow Cytometry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000473:pathology*; D008422:Materials Testing / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D044968:Regenerative Medicine / Q000379:methods*; D012756:Sheep; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014182:Transplantation, Autologous; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D019096:Vitronectin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005340:Fibrinogen