Microfluidic systems for stem cell-based neural tissue engineering

Abstract

Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a “brain-on-a-chip”. In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

μNeurocircuitry: Establishing in vitro models of neurocircuits with human neurons

“…The Campenot chamber, formed with a plastic divider affixed to a glass slide by silicone grease, sections of areas of culture while allowing axons to project through a series of channels created in a collagen layer 11,12 . More recently, approaches using soft lithography have produced more precisely defined channels and compartment structures 13,14 . These microfluidic devices have enabled studies of axonal injury 15–17 , axon pathfinding 18 and cellular migration 19 .…”

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

“…Current evidence suggests that three-dimensional (3D) culture techniques provide a distinct advantage for the maintenance and expansion of neurogenic neural stem cells (NSCs). Methods for 3D cell culture include the use of nano-carriers, microencapsulation, microisolation chambers (MICs), and cellular aggregates or organoids (reviewed in 36). Cellular aggregates and MICs are particularly amenable to the culturing of neural cells in 3D.…”

Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three‐Dimensional Hydrogels

“…For example, the advent of three‐dimensional culture systems has yielded tremendous insights in biology that were previously difficult or impossible to observe with traditional two‐dimensional culture systems (Kolesky, Homan, Skylar‐Scott, & Lewis, ; Laschke & Menger, ). Moreover, the use of perfusion devices, which can deliver media throughout a tissue construct, has been instrumental in overcoming the limits of gas and nutrient diffusion that would otherwise lead to necrosis (Gao et al., ; Huang et al., ; Karimi et al., ; Prodanov et al., ; Roberts, DiVito, Ligler, Adams, & Daniele, ; Zhang, Wang, Hui, Qiu, & Wang, ). However, the use of these perfusion approaches to control soluble factor delivery, and therefore morphogen presentation to embedded cells, has not been explored in great depth.…”

“…Current Protocols in Stem Cell Biology can deliver media throughout a tissue construct, has been instrumental in overcoming the limits of gas and nutrient diffusion that would otherwise lead to necrosis (Gao et al, 2017;Huang et al, 2011;Karimi et al, 2016;Prodanov et al, 2016;Roberts, DiVito, Ligler, Adams, & Daniele, 2016;Zhang, Wang, Hui, Qiu, & Wang, 2017). However, the use of these perfusion approaches to control soluble factor delivery, and therefore morphogen presentation to embedded cells, has not been explored in great depth.…”