Engineering of a Biomimetic Pericyte-Covered 3D Microvascular Network

Abstract

Pericytes enveloping the endothelium play an important role in the physiology and pathology of microvessels, especially in vessel maturation and stabilization. However, our understanding of fundamental pericyte biology is limited by the lack of a robust in vitro model system that allows researchers to evaluate the interactions among multiple cell types in perfusable blood vessels. The present work describes a microfluidic platform that can be used to investigate interactions between pericytes and endothelial cells (ECs) during the sprouting, growth, and maturation steps of neovessel formation. A mixture of ECs and pericytes was attached to the side of a pre-patterned three dimensional fibrin matrix and allowed to sprout across the matrix. The effects of intact coverage and EC maturation by the pericytes on the perfused EC network were confirmed using a confocal microscope. Compared with EC monoculture conditions, EC-pericyte co-cultured vessels showed a significant reduction in diameter, increased numbers of junctions and branches and decreased permeability. In response to biochemical factors, ECs and pericytes in the platform showed the similar features with previous reports from in vivo experiments, thus reflect various pathophysiological conditions of in vivo microvessels. Taken together, these results support the physiological relevancy of our three-dimensional microfluidic culture system but also that the system can be used to screen drug effect on EC-pericyte biology.

Pericytes Contribute to Dysfunction in a Human 3D Model of Placental Microvasculature through VEGF‐Ang‐Tie2 Signaling

“…Representative data from multiple experiments show drastic differences in vascular area, branch geometry, and overall network connectivity between HPP and HLF cocultures, as observed daily by confocal microscopy. [25,29] We postulated that differences between stromal cell interactions and vascular growth could be due to cell specific differences in cytokine expression. Similar decreases in vessel density and diameter have been shown with HUVEC-pericyte cultures in 3D angiogenesis assays.…”

Biomimetic on-a-chip platforms for studying cancer metastasis

“…Proliferating ECs in the surrounding matrix form new sprouts, and these sprouts make loops to become a vascular lumen [23]. There have been on-a-chip models that recapitulate hallmarks of the angiogenesis, such as vascular sprouting [18 •• ,24], network formation [20,21], perfused lumen formation [18 •• ,19,21], and maturation [25,26]. For example, Nguyen et al .…”

“…Another recent paper by Kim et al . employed human placental pericytes, and showed pericyte coverage on their 3D microvascular network [26]. …”

Pericyte-targeting drug delivery and tissue engineering

“…Interestingly, the ratio of ECs to PCs varies from 1:1 in neural tissue to 10:1 in skeletal muscle, which makes PCs attractive for investigation in the field of tissue engineering. 15 An isolated model for investigating the specific interaction between ECs and PCs has been demonstrated using a threedimensional microfluidic system by Kim et al 16 Compared with monoculture of ECs, coculture of PCs and ECs showed an increased number of junctions and branches, reduced diameter, and decreased permeability. Defined coculture and microfluidic model system of ECs, and PCs may be employed further to effectively screen PC-specific drugs for their effect on various biochemical factors.…”