Stem Cells and Extracellular Matrices for Cardiovascular Tissue Engineering

Cardiovascular disease is a leading cause of death in the United States.   In particular, myocardial infarction and peripheral arterial disease (PAD) are characterized by tissue ischemia due to the occlusion of arteries that supply blood to the heart or limbs, respectively.  In situ and in vitro tissue engineering strategies using stem cells and biomaterials have shown tremendous promise for cardiovascular repair.  Using adult bone marrow-derived mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), the therapeutic efficacy of these cells when delivered in situ into ischemic tissues were assessed by functional measurements, immunohistochemistry, and non-invasive imaging for cell survival.   These studies show a significant improvement in neovascularization when therapeutic cells and/or extracellular matrices (ECMs) were delivered to ischemic tissues after myocardial infarction or hindlimb ischemia.  Besides the in situ method, in vitro approaches to create engineered tissues that mimic the structure of native ECMs is promising.  Using parallel-aligned nanofibrillar matrices that mimic the structure of native collagen fibrils, engineered muscle constructs and vascular endothelium were fabricated and characterized.  Parallel alignment of the underlying matrix guided the alignment and fusion of myoblasts in the direction of the fibrils to create globally aligned myotube constructs.  Aligned nanofibrous collagen scaffolds not only induced endothelial cell alignment, but also better mimicked healthy endothelial cells that resist monocyte adhesion.  These studies highlight the utility of tissue engineering strategies for cardiovascular repair.