title: Engineering bioartificial tracheal tissue using hybrid fibroblast-mesenchymal stem cell cultures in collagen hydrogels.
abstract: We aimed at providing the first in vitro and in vivo proof-of-concept for a novel tracheal tissue engineering technology. We hypothesized that bioartificial trachea (BT) could be generated from fibroblast and collagen hydrogels, mechanically supported by osteogenically-induced mesenchymal stem cells (MSC) in ring-shaped 3D-hydrogel cultures, and applied in an experimental model of rat trachea injury. Tube-shaped tissue was constructed from mixtures of rat fibroblasts and collagen in custom-made casting molds. The tissue was characterized histologically and mechanically. Ring-shaped tissue was constructed from mixtures of rat MSCs and collagen and fused to the tissue-engineered tubes to function as reinforcement. Stiffness of the biological reinforcement was enhanced by induction of osteogeneic differentiation in MSCs. Osteogenic differentiation was evaluated by assessment of osteocalcin (OC) secretion, quantification of calcium (Ca) deposit, and mechanical testing. Finally, BT was implanted to bridge a surgically-induced tracheal defect. A three-layer tubular tissue structure composed of an interconnected network of fibroblasts was constructed. Tissue collapse was prevented by the placement of MSC-containing ring-shaped tissue reinforcement around the tubular constructs. Osteogenic induction resulted in high OC secretion, high Ca deposit, and enhanced construct stiffness. Ultimately, when BT was implanted, recipient rats were able to breathe spontaneously.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. naitoh@naramed-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naito
authors.forename: Takashi
authors.initials: T
authors.lastname: Tojo
authors.forename: Michitaka
authors.initials: M
authors.lastname: Kimura
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Dohi
authors.forename: Wolfram-Hubertus
authors.initials: WH
authors.lastname: Zimmermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
authors.forename: Shigeki
authors.initials: S
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012680:Sensitivity and Specificity; D023822:Tissue Engineering / Q000379:methods*; D014132:Trachea / Q000293:injuries / Q000601:surgery*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen