CD166pos Subpopulation From Differentiated Human ES and iPS Cells Support Repair of Acute Lung Injury期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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CD166pos Subpopulation From Differentiated Human ES and iPS Cells Support Repair of Acute Lung Injury

Authors:	Boon Seng Soh Dahai Zheng Julie Su Li Yeo Henry He Yang Shi Yan Ng Lan Hiong Wong Wencai Zhang Pin Li Massimo Nichane Atasha Asmat Poo Sing Wong Peng Cheang Wong Lin Lin Su Sakis A Mantalaris Jia Lu Wa Xian Frank McKeon Jianzhu Chen Elaine Hsuen Lim Bing Lim

Institution:	1. Department of Stem Cell and Developmental Biology, Genome Institute of Singapore, Genome, Singapore;2. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA;3. Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore, Singapore;4. Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;5. Cancer Institute of Singapore, National University of Singapore, Singapore, Singapore;6. National University Heart Centre Singapore, National University Hospital, Singapore, Singapore;7. Mount Elizabeth Medical Centre, Singapore, Singapore;8. Department of Obstetrics and Gynecology, National University Hospital, Singapore, Singapore;9. Department of Chemical Engineering and Chemical Technology, Faculty of Engineering, South Kensington Campus, Imperial College London, London, UK;10. Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Singapore;11. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;12. Institute of Molecular Biology, A-STAR, Singapore, Singapore;13. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA;14. The Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;15. Department of Respiratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore;16. Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Abstract:	Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient''s own iPS cells to prevent immune rejection which arise from allogenic transplantation.

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