Engineers grow realistic human tissues for drug discovery and testing
Researchers from the University of Toronto Faculty of Applied Science & Engineering (Canada) have developed a novel way to grow realistic human tissue outside the body, providing a powerful new platform for drug discovery and testing, and with potential applications for eventual repair or replacement of damaged organs.
A team from the University of Toronto Faculty of Applied Science & Engineering (Canada) have developed a novel technique for growing realistic human tissues outside of the body, a step that could have significant uses for drug discovery and testing and may eventually lead to production of replacement organs.
The researchers are one of several teams globally striving to find ways to grow human tissues in the laboratory. They have developed novel techniques for the manufacture of tiny, intricate scaffolds, on which individual cells can grow. By culturing these cells in artificial environments designed to mimic the human body, they can produce cells and tissues far more similar to real organs than those grown in a flat petri dish.
The ‘person-on-a-chip’ technology, dubbed AngioChip, is the latest in the team’s list of innovative tissue engineering creations. "It's a fully three-dimensional structure complete with internal blood vessels," explained Milica Radisic, who led the study. "It behaves just like vasculature, and around it there is a lattice for other cells to attach and grow."
Boyang Zhang, a graduate student and team member, built the scaffold out of a polymer called POMaC, which is both biodegradable and biocompatible. It is constructed from a series of thin layers, and then stamped with a pattern of 50–100 micrometer-wide channels. The layers are then stacked into a 3D structure of synthetic blood vessels, which are treated with UV lights as each layer is added to cross-link the polymer and bond it to the preceding layer.
The structure is finally bathed in liquid containing living cells, which swiftly adhere to the channels and begin growing just as they would in the human body. "Previously, people could only do this using devices that squish the cells between sheets of silicone and glass," described Radisic. "You needed several pumps and vacuum lines to run just one chip. Our system runs in a normal cell culture dish, and there are no pumps; we use pressure heads to perfuse media through the vasculature. The wells are open, so you can easily access the tissue."
The researchers have utilized the platform to construct model heart and liver tissue capable of functioning just like the real thing. "Our liver actually produced urea and metabolized drugs," continued Radisic. The system also allows for the blood vessels of two artificial organs to be connected, so that scientists can model both the organs and the interaction between them. The team has even observed injected white blood cells squeeze through gaps in the vessel walls, just as they would in human tissue.
AngioChip therefore has potential applications in pharmaceutical testing, avoiding the cost and ethical concerns of testing methods such as clinical trials and animal testing. "In the last few years, it has become possible to order cultures of human cells for testing, but they're grown on a plate, a two-dimensional environment," Radisic described. "They don't capture all the functional hallmarks of a real heart muscle, for example."
Radisic believes that, in the future, her team’s lab-grown tissues could be implanted into the human body to repair disease-damaged organs. The cells used to seed the platform could be provided by the patient, providing new tissue genetically identical to the old and reducing the risk of organ rejection. In its current form, the AngioChip can be implanted into a living animal, with the polymer scaffolding biodegrading naturally over a period of months.
The next stage will be to develop high-throughput manufacturing methods to create many copies at once, as each AngioChip is currently made by hand. However, the future applications are clear to Radisic: "It really is multifunctional, and solves many problems in the tissue engineering space," she concluded. "It's truly next-generation."
Zhang B, Montgomery M, Chamberlain MD et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat. Mater. doi:10.1038/nmat4570 (2016) (Epub ahead of print); http://news.engineering.utoronto.ca/person-on-a-chip-u-of-t-engineers-create-lab-grown-heart-and-liver-tissue-for-drug-testing-and-more/?_ga=1.81716373.382618477.1454691581