title: Differentiation of lung stem/progenitor cells into alveolar pneumocytes and induction of angiogenesis within a 3D gelatin--microbubble scaffold.
abstract: The inability to adequately vascularize tissues in vitro or in vivo is a major challenge in lung tissue engineering. A method that integrates stem cell research with 3D-scaffold engineering may provide a solution. We have successfully isolated mouse pulmonary stem/progenitor cells (mPSCs) by a two-step procedure and fabricated mPSC-compatible gelatin/microbubble-scaffolds using a 2-channel fluid jacket microfluidic device. We then integrated the cells and the scaffold to construct alveoli-like structures. The mPSCs expressed pro-angiogenic factors (e.g., b-FGF and VEGF) and induced angiogenesis in vitro in an endothelial cell tube formation assay. In addition, the mPSCs were able to proliferate along the inside of the scaffolds and differentiate into type-II and type-I pneumocytes The mPSC-seeded microbubble-scaffolds showed the potential for blood vessel formation in both a chick chorioallantoic membrane (CAM) assay and in experiments for subcutaneous implantation in severe combined immunodeficient (SCID) mice. Our results demonstrate that lung stem/progenitor cells together with gelatin microbubble-scaffolds promote angiogenesis as well as the differentiation of alveolar pneumocytes, resulting in an alveoli-like structure. These findings may help advance lung tissue engineering.
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: tyling@ntu.edu.tw.
authors.forename: Thai-Yen
authors.initials: TY
authors.lastname: Ling
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Liang
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yung-Kang
authors.initials: YK
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sing-Yi
authors.initials: SY
authors.lastname: Gu
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hung-Kuan
authors.initials: HK
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Choa-Chi
authors.initials: CC
authors.lastname: Ho
authors.affiliation: Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan; Division of Neonatology, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Po-Nien
authors.initials: PN
authors.lastname: Tsao
authors.affiliation: Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Tung
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chiung-Hsiang
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan; Institute of Physics, Academia Sinica, Taipei, Taiwan.
authors.forename: Keng-Hui
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D005780:Gelatin / Q000737:chemistry*; D008168:Lung / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D045423:Microbubbles; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005780:Gelatin
keywords: Alveoli; Angiogenesis; Lung stem/progenitor cells; Microbubble-scaffold; Pneumocytes