Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, United States
Elizabeth K Johnston
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, United States
Jun Jie Tan
Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia
Jacqueline M Bliley
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, United States; Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, United States
Adam W Feinberg
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, United States; Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, United States
Donna B Stolz
Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States
Ming Sun
Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States
Piyumi Wijesekara
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, United States
Finn Hawkins
Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, United States
The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human-induced pluripotent stem cells (hiPSCs) via temporal specific tuning of WNT and nodal signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (μTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage μT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect that our multilineage differentiation model will offer an experimentally tractable system for investigating human cardio-pulmonary interaction and tissue boundary formation during embryogenesis.
