Spheroid three-dimensional culture enhances Notch signaling in cardiac progenitor cells

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iomaterials for 3D Cell Biology Research Letter

Spheroid three-dimensional culture enhances Notch signaling in cardiac progenitor cells Arianna Mauretti†, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, The Netherlands Fabrizio Rossi†, Department of Molecular Medicine, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy Noortje A. M. Bax, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, The Netherlands Carmen Miano, Department of Molecular Medicine, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy Fabio Miraldi, Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy Marie José Goumans, Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands Elisa Messina, Department of Molecular Medicine, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; Department of Pediatrics and Pediatric Neuropsychiatry, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy Alessandro Giacomello, Department of Molecular Medicine, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy Carlijn V. C. Bouten, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, The Netherlands Cecilia Sahlgren, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, The Netherlands; Cell biology, Faculty of Science and Engineering, Åbo Akademi University, FI-20520 Turku, Finland; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland Address all correspondence to Arianna Mauretti at [email protected] (Received 13 April 2017; accepted 21 August 2017)

Abstract Cardiac progenitor cells (CPCs) are a promising candidate for cardiac regeneration, and the interaction between CPCs and their microenvironment can influence their regenerative response. Notch signaling plays a key role in cell fate decisions in the developing and adult heart. Here, we investigated the effect of three-dimensional (3D) spheroid culture, as a model of the 3D microenvironment, on Notch in fetal and adult human CPCs, under room air (20%) and physiological (5%) oxygen tension. Notch signaling is enhanced in 3D spheroids; spheroid culture under 5% O2 further increases Notch signaling enhancement, and might ultimately improve the regenerative potential of