Guided Self-Assembly of ES-Derived Lung Progenitors into Biomimetic Tube Structures That Impact Cell Differentiation.
John P Soleas, Linwen Huang, Elisa D'Arcangelo, Maria Cristina Nostro, Thomas K Waddell, Alison P McGuigan, Golnaz Karoubi
Author Information
John P Soleas: Institute for Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
Linwen Huang: Institute for Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
Elisa D'Arcangelo: Institute for Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
Maria Cristina Nostro: McEwen Stem Cell Institute, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada.
Thomas K Waddell: Institute for Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
Alison P McGuigan: Institute for Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada. ORCID
Golnaz Karoubi: Latner Thoracic Surgery Research Laboratories, Toronto General Hospital, 101 College Street, Toronto, ON M5G 1L7, Canada.
Chemically directed differentiation of pluripotent stem cells (PSCs) into defined cell types is a potent strategy for creating regenerative tissue models and cell therapies. In vitro observations suggest that physical cues can augment directed differentiation. We recently demonstrated that confining human PSC-derived lung progenitor cells in a tube with a diameter that mimics those observed during lung development results in the alteration of cell differentiation towards SOX2SOX9 lung cells. Here we set out to assess the robustness of this geometric confinement effect with respect to different culture parameters in order to explore the corresponding changes in cell morphometry and determine the feasibility of using such an approach to enhance directed differentiation protocols. Culture of progenitor cells in polydimethylsiloxane (PDMS) tubes reliably induced self-organization into tube structures and was insensitive to a variety of extracellular matrix coatings. Cellular morphology and differentiation status were found to be sensitive to the diameter of tube cells that were cultured within but not to seeding density. These data suggest that geometric cues impose constraints on cells, homogenize cellular morphology, and influence fate status.
