Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering

Abstract

Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine – including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering – have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs. In this review we examine recent advances in the field of stem cell-derived vasculature, providing an overview of stem cell technologies as a source for vascular cell types and then focusing on their use in three primary areas: studies of vascular development and angiogenesis, improved disease modeling, and the engineering of vascularized constructs for tissue-level modeling and cell-based therapies.

A novel scale‐down cell culture and imaging design for the mechanistic insight of cell colonisation within porous substrate

“…As the scale‐down design has full control of the cell culture environment, it is possible to evaluate other biochemical, biomechanical properties, and multivariate bioactive molecules (Yang et al. , ; Lowenthal & Gerecht, ) in the presence or absence of specific elementary structures. By culturing different types of cells on the modular substrate, the close spatial relationships and interactions between the cultivated cells, and its influences on the proliferation and migration of each cell type can be also monitored and assessed.…”

“…Thus, the 3D CCISs provided a unique, insightful and simplistic platform to investigate the regulatory functions of elementary structures in 3D matrices especially the cell-scaffold and cell-cell interactions at macro-, micro-and nanoscales, which could be difficult to obtain using other cell culture and analysis methods. As the scale-down design has full control of the cell culture environment, it is possible to evaluate other biochemical, biomechanical properties, and multivariate bioactive molecules Lowenthal & Gerecht, 2016) in the presence or absence of specific elementary structures. By culturing different types of cells on the modular substrate, the close spatial relationships and interactions between the cultivated cells, and its influences on the proliferation and migration of each cell type can be also monitored and assessed.…”

“…, ; Yang et al. , ; Lowenthal & Gerecht, ). Monitoring cells infiltrated deep inside 3D scaffolds using conventional optical microscopes is also hardly achievable simply due to their limited focus depth compared with the size of most scaffolds (from mm to cm) (Baradez & Marshall, ; Sun et al.…”

“…Overall, at the core of all these translational challenges is the mechanistic understanding of tissue formation, but thorough investigation of the aforementioned relationships at different levels and the underpinning biological processes of TE based on current tissue culture and analysis methodologies is still a challenging task. First of all, it is almost impossible to distinguish the regulatory functions of each individual architectural and topographic features at nano-, microand macroscales, as well as other biochemical and biomechanical properties because of their coexistence in 3D biomatrices (Lin et al, 2014;Yang et al, 2014;Lowenthal & Gerecht, 2016). Monitoring cells infiltrated deep inside 3D scaffolds using conventional optical microscopes is also hardly achievable simply due to their limited focus depth compared with the size of most scaffolds (from mm to cm) (Baradez & Marshall, 2011;Sun et al, 2011).…”

Mechanistic Insights of Cells in Porous Scaffolds via Integrated Culture Technologies

“…However, the introduction of these in vitro models are a trade-off between the value of obtaining physiologically relevant data against their through-put as they are usually more labour intensive [11]. Furthermore, it is problematic to utilise tissue models for thorough investigation of the aforementioned complex relationships during tissue regeneration, as it is difficult to distinguish the regulatory functions of each individual architectural features at nano-and micro-scales, as well as other biochemical and biomechanical properties in the 3D culture environments [12][13][14][15]. To bridge the gap between the 2D and 3D culture technologies, we have recently developed a 3D CCIS (3D cell culture and imaging system) [15].…”