Vascular microphysiological systems to model diseases

Abstract

Human vascular microphysiological systems (MPS) represent promising three-dimensional in vitro models of normal and diseased vascular tissue. These systems build upon advances in tissue engineering, microfluidics, and stem cell differentiation and replicate key functional units of organs and tissues. Vascular models have been developed for the microvasculature as well as medium-size arterioles. Key functions of the vascular system have been reproduced and stem cells offer the potential to model genetic diseases and population variation in genes that may increase individual risk for cardiovascular disease. Such systems can be used to evaluate new therapeutics options.

Challenging the status quo: a framework for mechanistic and human-relevant cardiovascular safety screening

“…Rapid development of in vitro modeling systems that incorporate human induced pluripotent stem cells (iPSC)-derived cardiomyocytes, smooth muscle and endothelial cells offer opportunities to assess Tier 1 bioactivities for their cell, tissue or organ effects (i.e., Tier II assessment) ( Dick et al, 2010 ; Rana et al, 2012 ; Doherty et al, 2013 ; Pointon et al, 2013 ; Grimm et al, 2018 ; Gintant et al, 2019 ). Some of these systems are rapidly becoming more physiologically-relevant incorporating important elements of 3D architecture, multiple cell types, contractile function, rhythmicity and microfluidic shear ( Ogunrinade et al, 2002 ; Fernandez et al, 2016 ; Huebsch et al, 2016 ; Truskey, 2016 ; Atchison et al, 2017 ; Hoang et al, 2018 ; Zhang et al, 2020 ). An expanding portfolio of endpoints like contractile rate, action potential generation, rhythm and force; ATP generation, markers of oxidative stress, smooth muscle contraction or relaxation; as well as cell morphology and viability provide direct lines of sight to recognized responses to cardiac or vascular injury.…”

Microphysiological systems: What it takes for community adoption

“…12 Ultimately, this 5-year program provided proof of principle that tissue chips could accurately recapitulate human physiology and drug responses. 12 While DARPA funding ended in 2017, the NIH MPS program has continued and since evolved to look at various tissue chip technology end uses, including disease modeling and efficacy testing; [74][75][76][77][78][79] modeling opioid use disorders; using tissue chips to improve clinical trial design and execution; and creating independent validation/testing centers 59,[80][81][82] plus a publicly accessible database 83,84 for MPS data. In addition to the NIH and DARPA MPS programs, the US Environmental Protection Agency established the "Science to Achieve Results" (STAR) grant program, one goal of which is to further the development of organotypic culture models, including organs-on-chips (OoCs) for predictive toxicology.…”