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Issue 9, 2016
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Cardiomyocyte progenitor cell mechanoresponse unrevealed: strain avoidance and mechanosome development

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Abstract

For emerging cardiac regeneration strategies, it is essential to know if and how cardiac stem cells sense and respond to the mechanical stimuli provided by their environment in the beating heart. Here, we study the response to cyclic strain of undifferentiated and predifferentiated human cardiomyocyte progenitor cells (CMPCs), as well as the formation and activation of the cellular structures involved in mechanosensing, that we termed ‘mechanosome’. Once verified that the applied uniaxial cyclic strain (10%, 0.5 Hz) did not alter the cardiac lineage commitment and differentiation state of CMPCs, the cellular mechanoresponse to the applied strain was quantified by cellular orientation. While undifferentiated cells maintained their original (random) orientation, upon early cardiomyogenic differentiation (predifferentiated) CMPCs exhibited a distinct strain avoidance response after 48 h of cyclic straining. Interestingly, the mechanosome development and the activation of the mechanotransduction pathways also occurred with early cardiac differentiation of the CMPCs, regardless of the substrate or the applied cyclic strain. These results indicate that the mechanoresponse of CMPCs depends on the presence of a developed mechanosome, which only develops during early cardiomyogenic differentiation Our findings provide the first understanding of mechanotransduction in human CMPCs and as such can contribute to the improvement of cardiac regeneration strategies.

Graphical abstract: Cardiomyocyte progenitor cell mechanoresponse unrevealed: strain avoidance and mechanosome development

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Supplementary files

Article information


Submitted
23 Jun 2016
Accepted
24 Aug 2016
First published
01 Sep 2016

Integr. Biol., 2016,8, 991-1001
Article type
Paper

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