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Stem Cell Reports. 2015 Mar 10;4(3):419-30. doi: 10.1016/j.stemcr.2015.01.004. Epub 2015 Feb 5.

Acellular lung scaffolds direct differentiation of endoderm to functional airway epithelial cells: requirement of matrix-bound HS proteoglycans.

Author information

1
Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada.
2
Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
3
Program in Molecular Structure and Function, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
4
Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
5
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
6
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
7
Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
8
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada; Program in Molecular Structure and Function, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
9
Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada. Electronic address: martin.post@sickkids.ca.

Abstract

Efficient differentiation of pluripotent cells to proximal and distal lung epithelial cell populations remains a challenging task. The 3D extracellular matrix (ECM) scaffold is a key component that regulates the interaction of secreted factors with cells during development by often binding to and limiting their diffusion within local gradients. Here we examined the role of the lung ECM in differentiation of pluripotent cells in vitro and demonstrate the robust inductive capacity of the native lung matrix alone. Extended culture of stem cell-derived definitive endoderm on decellularized lung scaffolds in defined, serum-free medium resulted in differentiation into mature airway epithelia, complete with ciliated cells, club cells, and basal cells with morphological and functional similarities to native airways. Heparitinase I, but not chondroitinase ABC, treatment of scaffolds revealed that the differentiation achieved is dependent on heparan sulfate proteoglycans and its bound factors remaining on decellularized scaffolds.

PMID:
25660407
PMCID:
PMC4375883
DOI:
10.1016/j.stemcr.2015.01.004
[Indexed for MEDLINE]
Free PMC Article

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