Micro- and nanoscale control of the cardiac stem cell niche for tissue fabrication

Advances in stem cell (SC) biology have greatly enhanced our understanding of SC self-renewal and differentiation. Both embryonic and adult SCs can be differentiated into a great variety of tissue cell types, including cardiac myocytes. In vivo studies and clinical trials, however, have demonstrated major limitations in reconstituting the myocardium in failing hearts. These limitations include precise control of SC proliferation, survival and phenotype both prior and subsequent to transplantation and avoidance of serious adverse effects such as tumorigenesis and arrhythmias. Micro- and nanoscale techniques to recreate SC niches, the natural environment for the maintenance and regulation of SCs, have enabled the elucidation of novel SC behaviors and offer great promise in the fabrication of cardiac tissue constructs. The ability to precisely manipulate the interface between biopolymeric scaffolds and SCs at in vivo scale resolutions is unique to micro- and nanoscale approaches and may help overcome limitations of conventional biological scaffolds and methods for cell delivery. We now know that micro- and nanoscale manipulation of scaffold composition, mechanical properties, and three-dimensional architecture have profound influences on SC fate and will likely prove important in developing the next generation of "transplantable SC niches" for regeneration of heart and other tissues. In this review, we examine two key aspects of micro- and nanofabricated SC-based cardiac tissue constructs: the role of scaffold composition and the role of scaffold architecture and detail how recent work in these areas brings us closer to clinical solutions for cardiovascular regeneration.