Mechanical influences on cardiovascular differentiation and disease modeling.

Tissues are continuously exposed to forces in vivo, whether from fluid pressure in an artery from our blood or compressive forces on joints from our body weight. The forces that cells are exposed to arise almost immediately after conception; it is therefore important to understand how forces shape stem cell differentiation into lineage committed cells, how they help organize cells into tissues, and how forces can cause or exacerbate disease. No tissue is exempt, but cardiovascular tissues in particular are exposed to these forces. While animal models have been used extensively in the past, there is growing recognition of their limitations when modeling disease complexity or human genetics. In this mini review, we summarize current understanding of the mechanical influences on the differentiation of cardiovascular progeny, how the transduction of forces influence the onset of disease, and how engineering approaches applied to this problem have yielded systems that create mature-like human tissues in vitro in which to assess the impact of disease on cell function.