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Biomaterials. 2014 Jul;35(22):5660-9. doi: 10.1016/j.biomaterials.2014.03.074. Epub 2014 Apr 18.

Differentiation of lung stem/progenitor cells into alveolar pneumocytes and induction of angiogenesis within a 3D gelatin--microbubble scaffold.

Author information

1
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.
2
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
3
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
4
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
5
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
6
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.
7
Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan.
8
Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
9
Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
10
Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan; Institute of Physics, Academia Sinica, Taipei, Taiwan.
11
Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.

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.

KEYWORDS:

Alveoli; Angiogenesis; Lung stem/progenitor cells; Microbubble-scaffold; Pneumocytes

[Indexed for MEDLINE]

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