Cardiovascular Diseases and Stem Cell Modeling

Dear Colleagues,

The biological potency of pluripotent cells has emerged as a powerful tool to model disease processes, with seminal work laying the foundation for understanding cardiopathology from its potential origins within the womb to perinatal manifestation continuing on into adulthood. In particular, the discovery and identification of the Yamanaka reprogramming factors over a decade ago pioneered induced pluripotent stem cell (iPSC)-driven research that took advantage of iPSC ability to recapitulate critical hallmarks and processes of embryonic stem cell biology. With this competence for differentiation, cardiovascular research has benefited from iPSC work, with insights into innate mechanisms of cardiogenic regulation, the role of three dimensional architecture in fate commitment, and the paracrine contribution of secretome composition and extracellular vesicles.

Despite this technological advancement, there exist current limitations of iPSC technology that provide opportunities for growth and development. For example, investigating and defining mechanisms of cardiomyocyte maturation is an active and ongoing focus in the field, as iPSC-derived CM recapitulate a more immature phenotype that does not capture all qualities of mature cardiomyocytes. Recent exciting developments in the field suggest that metabolic supplementation with fatty acids efficiently promotes maturation, and can be considered along with electrical pacing and three dimensional scaffolding as critical factors essential to recapitulate adult cardiomyocyte phenotypes.

In the arena of vascular disorders, the generation of endothelial and smooth muscle cells (SMCs) to model disease has benefited from robust methods that result in mature endothelial and SMC populations. Furthermore, the heterogeneity within each vascular cell type can be recapitulated in culture, allowing researchers to calibrate protocols accordingly. As with cardiac differentiation paradigms, refinements that promote differentiation of iPSC-derived endothelial cells and SMCs have identified co-culture with supporting perivascular cells as essential for functional maturation.

Overall, work in the field is essential to build a robust foundation for the development of paradigms of cardiovascular regenerative medicine. With this in mind, the goal of this special issue therefore is to summarize contemporary knowledge regarding the use of stem cells to model cardiovascular diseases, highlight recent advances covering different aspects and applications of stem cell platforms in the context of understanding cardiovascular pathologies, and stimulate thought on future directions of the field.

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• cardiogenesis/vasculogenesis
• pluripotent cells
• human induced pluripotent stem cells
• pharmacological screening and disease modeling
• 3D scaffolding
• microenvironment
• extracellular vesicles
• epigenomic regulation
• transcriptome profiling
• disease proteomes/interactomes