Transcript Document

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