INNOVATION January-February 2016

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“What you can get into people now is so primitive,” says Willerth. “We’re injecting cells into injury back where we were with mice in 1999.” Currently, no good medical interventions exist that will reinstate function. The advent of stem-cell manipulation threw open the door to a new class of treatment. Although mammals cannot grow newmotor neurons to replace those damaged in the spine, research indicates that bodies can accept young, adaptable neurons and integrate them to repair the damage. Major steps to developing reliable regenerative medical treatments include growing new neurons, introducing them to the damaged site, and directing their growth as they assimilate into the body. Each step faces its own set of challenges. Willerth engineers neural tissue by combining stem cells with drug-releasing particles. Her lab, which focuses its efforts “more on the tool side” than the treatment side, creates imitation tissue for clinical trials to use in cell transplants. She works

with induced pluripotent stem cells— regular human cells, typically from skin or blood, reprogrammed to grow into any adult cell type. She prefers using induced cells to embryonic ones, because the former produce patient-specific cells and develop fewer tumours. A recent discovery found that successfully growing neurons depends on the culture’s medium, because it supplies both the chemical mix in which to grow cells and the structure on which nerve cells grow. Conventional methods rely on an unstructured two-dimensional substrate, but neurons naturally grow and intertwine in a three-dimensional world. Willerth’s lab creates cultures packed with miniature scaffolding. They use fibrin, a robust, versatile protein responsible for clotting blood, to make a gelatinous three- dimensional structure for young neurons to twine around, a bit like a trellis for vines. Fibrin’s bioactivity also boosts cell survival. Embedding fibrin scaffolds seeded with neurons into injury sites shows promising results. The protein lasts about two weeks, making it a good choice for mice but a poor one for humans, whose stem cells take two months to differentiate. Willerth is looking at synthetic scaffold options that humans can slowly and harmlessly metabolise. The third step, directing cell growth as it integrates into the body, requires chemical cues normally present during development. One strategy for establishing remote cell control involves enveloping the chemicals in microspheres and delivering them to dense clusters of pluripotent cells. To investigate its feasibility, Willerth encapsulated retinoic acid, a molecule critical for neural growth, in 10-micrometre spheres of a biodegradable polymer and introduced them to stem cell clusters. After several days, the team found that the retinoic acid was delivered consistently to young cells throughout each cluster and the cells subsequently developed into neurons. The results, published this year, show the method has potential for neural tissue-engineering applications and for developing cells within patients and other living subjects. Once she refines integration methods, Willerth wants to work with Blusson Spinal Cord Centre in Vancouver to apply it to injury models. This “tool” may be early in its development, but it already seems like a

screwdriver among hammers. Moreover, considering how loss of mobility and consequent barriers to education and income make people with spinal injuries up to five times more likely to die prematurely, such a promising advance is welcome. In the last year alone, BC engineers have helped make heart surgery faster than an oil change, bionic hands cheaper than a fancy dinner, and have crafted a minuscule trellis that feeds budding neurons as they grow on it. These projects—just a handful of the many BC ventures in biomedical engineering—represent the creative advances in biochemistry, materials science, miniaturising, and software and systems design that characterise the passion of APEGBC engineers. v Stephanie Willerth, P.Eng., and her team engineer nerve tissue from stem cells. T op : Cells derived from human-induced pluripotent stem cells (neurons: green, cell nuclei: blue, neural progenitors: red). B ottom : A neural aggregate contains drug- releasing microspheres ( inset ) that help stem cells differentiate into neurons (green). P hotos : W illerth lab , U niversity of V ictoria

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