Stephanie Willerth presenting at the Till and McCulloch Meetings 2018
This year, the annual Till & McCulloch Meetings ended with a plenary session on the “next generation of regenerative medicine” to keep attendees thinking forward as they headed back home.
While all of them were incredibly exciting, I was particularly struck by the futuristic techniques presented by Dr. Stephanie Willerth, who showed fantastic images and videos of her lab’s work 3D printing brain cells.
Beyond being a really cool technique, bioprinting is an attractive approach for future regenerative medicines. The “bioink” of the printer can be modified depending on the cell type being cultured so that it has the right viscosity and polymerizes to appropriate stiffness upon printing.
The Willerth lab tested different combinations of five different small molecules in a fibrin-based bioink. Each of these five molecules were previously shown to be helpful in directing pluripotent cells to a dopaminergic neuron fate. While dopamine neurons are the primary cell type lost in Parkinson’s Disease, producing mature dopamine neurons in a time and cost effective manner, and getting them to integrate in the brain, remain challenges.
In all small molecule conditions the Willerth lab saw proliferation of cells in the bioink and a high viability of 85-95 percent after printing — a significant improvement over previous attempts in the literature. After 30 days of culture in 3D-printed, layered ring structures, the stem cells were found to have differentiated sufficiently to express mature neuronal markers. In addition to neuronal markers they also identified astrocytes, an important cell type in the brain critical for the survival of neurons.
But the most exciting feature of bioprinting is not that you can make these cells, but that they can be spatially distributed as desired to pattern tissues in an optimal way. This means that using this technology we could print out the cell types we want and arrange them exactly how we want them. This feature can help us get closer to creating tissues in the lab that have the same organization as the tissues in our bodies – something difficult to do in a dish.
Plus her group recently published work showing that microspheres-encapsulated drugs (a microsphere is a hollow sphere usually constructed from a protein or synthetic polymer), with time-controlled release, could also be patterned in bioink. These two findings, plus the 3D structure after printing, means this technology could allow us to pattern cells specifically as desired and control the timing with which they receive specific chemicals, which would hopefully normalize and automate future cell manufacturing processes.
In the future, a biodegradable bioink could be used so that after transplantation it dissolves, leaving only the cells in the correct formation. But these bioprinted structures can also be useful for drug discovery.
After reading and reviewing her textbook last year on neural tissue engineering, I went into this talk with high expectations… she didn’t disappoint!
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