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Cell-matrix interactions in cardiac progenitor cell niche Arianna Mauretti, Cecilia Sahlgren, Frank Baaijens, Carlijn Bouten Introduction After myocardial infarction (MI), the contractility of the heart is severely compromised, and a scar tissue is formed. Cardiac progenitor cells (CPCs) can be injected in the injured myocardium, give rise to new cardiomyocytes and repair the damaged heart [1;3]. Methods Figure 1: Integration of the transplanted cells in the host tissue and their response to the biomechanical stimuli provided by the heart are crucial for a good outcome of the therapy. Upon mechanical stimulation, focal adhesion (FA) proteins are recruited at cell-matrix adhesion sites, allowing cells to sense and respond to mechanical cues [1;2]. Figure 2: L9TB CPCs were cultured and differentiated for 14 days [4]. Uniaxial cyclic strain with 10% strain and 0.5Hz was applied to undifferentiated and predifferentiated CPCs seeded on Bioflex membranes coated with collagen IV for 48h. Static samples were used as control. The substrate influences the development of FAs in CPCs Differentiation but not strain induces FA development in CPCs Figure 4: Vinculin expression in undifferentiatied and predifferentiated CPCs over time. On collagen IV, ECM protein of the heart tissue, we observed a significantly faster FA development in predifferentiated than in undifferentiated CPCs, which was not observed when cells were seeded on gelatin coated glasses. gel= gelatin; coll=collagen IV coating. Scale bar 100 μm. Conclusions and future outlook Figure 3: Cardiomyogenic differentiation favored FA formation and maturation, whereas no effect of the strain on FA development at both protein and gene expression was observed. Scale bar 100μm. Overall, this 2D study is a first step towards the understanding of CPC behavior upon mechanical stimuli, and can represent the basis for future experiments in 3D, more niche-like, environments. Signaling interference studies will allow identifying the active players in CPC response to mechanical cues. References: /Department of Biomedical Engineering [1] Pijnappels DA et al., Ann. N.Y. Acad. Sci. 2010;1188:7-14 [2] Kanchanawong P at el., Nature 2010;468:580-586 [3] Smits AM et al., Nature Protocols 2009;4(2):232-243 [4] Bax N, Marion MH et al., JMCC 2012;53:497–508