期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 4, 期 11, 页码 1265-1274出版社
OXFORD UNIV PRESS
DOI: 10.5966/sctm.2015-0062
关键词
Adult lung stem cells; Mesenchymal stem cells; Pulmonary fibrosis; Spheroid cell culture
资金
- National Institutes of Health
- American Heart Association
- North Carolina State University (NC State) Chancellor's Faculty Excellence Program
- NC State Center for Comparative Medicine and Translational Researches
- NC State Kenan Foundation Regenerative Medicine Grant
Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration.
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