CD166(pos) subpopulation from differentiated human ES and iPS cells support repair of acute lung injury.

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.

• 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
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 20 Issue 12 Pg. 2335-46 (Dec 2012) ISSN: 1525-0024 [Electronic] United States
• PMID: 22968480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ALCAM protein, human
• Antigens, CD
• Cell Adhesion Molecules, Neuronal
• Fetal Proteins

Topics

• Acute Lung Injury (genetics, metabolism, therapy)
• Animals
• Antigens, CD (metabolism)
• Cell Adhesion Molecules, Neuronal (metabolism)
• Cell Differentiation (genetics, physiology)
• Cell Line
• Embryonic Stem Cells (cytology, metabolism, physiology, transplantation)
• Fetal Proteins (metabolism)
• Flow Cytometry
• Humans
• Immunohistochemistry
• Induced Pluripotent Stem Cells (cytology, metabolism, physiology, transplantation)
• Mice