Earlier this year, the University of Toronto’s Institute of Biomaterials and Biomedical Engineering (IBBME) published its Annual Report, chock full of impressive numbers about enrolment, new programs and research published by its esteemed faculty. (If you’re curious, you can read it for yourself.) In response, I summarized the regenerative medicine research here.
But I only covered half the story. Some IBBME faculty are focusing on enabling technologies – such as tools, methods, devices and innovative technologies – that enable regenerative medicine to succeed. It’s essential research and could include such things as computational modeling for engineering functional 3D tissues; customizable scaffolds for cells; novel bioreactors (think of Dr. Peter Zandstra’s Fed-Batch bioreactor system); and more.
With thanks to our partners at IBBME at the University of Toronto, please enjoy these research summaries from work that was published in 2016.
Understanding a key roadblock behind nanoparticle cancer drug delivery
The emerging field of nanomedicine holds great promise in the battle against cancer. Tiny particles similar in size to protein molecules can be customized to carry tumour-targeting drugs and destroy cancer cells without harming healthy tissue.
But, when nanoparticles are administered into the body, more than 99 percent of them become trapped in non-targeted organs, such as the liver and spleen. These nanoparticles are not delivered to the tumour to carry out their intended function.
Professor Warren Chan, Canada Research Chair in Bionanotechnology, and recent MD/PhD graduate Dr. Kim Tsoi (IBBME PhD 1T6) partnered with researchers from the University of Toronto’s Faculty of Medicine, Department of Physics and the University Health Network to figure out how the liver and spleen trap intact nanoparticles as they move through the organ.
The team discovered that as nanoparticles move through the liver sinusoid, the flowrate slows down 1,000 times, which increases the interaction between the nanoparticles and all types of liver cells. This was a surprising finding because the thought at the time was that Kupffer cells, responsible for toxin breakdown in the liver, would be the ones that gobble up the particles. In contrast, this study found that liver B-cells and liver sinusoidal endothelial cells are also involved and that the cell phenotype also matters. The results of their four-year study, titled “Mechanism of hard-nanomaterial clearance by the liver” was published on August 15, 2016 in the journal Nature Materials.
Apollo-NADP+: a new cell imaging technique for diabetes, cancer and more
Graduate students William Cameron and Cindy Bui from Professor Jonathan Rocheleau’s Quantitative Microscopy, Microfluidics and Metabolism Lab spearheaded a new way to visualize biochemical reactions in cells. By offering new insight into how human cells work—or, in the case of diseased cells, how they malfunction—the technique could advance the study of diabetes, cancer and other conditions.
In collaboration with investigators from the Toronto General Research Institute, they invented a biological sensor based on fluorescent proteins that glow in response to laser light. Specifically, it is a kind of molecular tag that binds to and illuminates NADP+ , a molecule in our cells involved with many biological functions, from breaking down fats and proteins to protecting against stress. When NADP+ doesn’t work properly, it can trigger undesired effects that result in conditions such as diabetes and arthritis.
The novelty in the team’s new sensor, called Apollo-NADP+ , is that it responds using a single colour while previous techniques typically require two different colours to conduct proper tracking. Prior to their invention, tracking two molecules would require four colours, and three would require six, resulting in microscope slides that resembled an incomprehensible kaleidoscope.
Apollo-NADP+ responds with a change in polarization of light emitted, as opposed to a change in colour when a molecule increases in concentration, and can be detected using light filters similar to those found in 3D movie eyeglasses. The team can also tune the single colour output into a variety of wavelengths, allowing for more flexibility in how responses are measured within the cell, paving the way for new types of observations that can be made about how cells use or misuse their NADP+ supply.
Their work, titled “Apollo-NADP+ : A spectrally tunable family of genetically encoded sensors for NADP+ ” was published on February 15, 2016 in the journal Nature Methods. The team also subsequently released their sensor design in open source as a blueprint for other investigators to adapt to their own research.
Battery-sized microscope gives new insights into brain activity during seizure
(I think the following enabling technology might have applications for regenerative medicine in the future, hence I’m including it here.)
PhD candidates Illya Sigal and Dene Ringuette from Professor Ofer Levi’s lab developed a miniature microscope—about the size of a triple-A battery—that can be used to peer into a rodent’s brain during an epileptic seizure without anesthesia. The technique allows for concurrent monitoring of brain blood flow and blood oxygenation in awake, freely-behaving rats, and could lead to more effective drug testing and treatment development.
In partnership with researchers at the Sunnybrook Research Institute and the University Health Network’s Krembil Research Institute, they designed and built a scaled-down optical microscope comprising of a skull adapter plate, an imaging tube and a laser light source.
The microscope measured 40 millimeters in length and 12 millimeters in diameter and weighed 15 grams including the base plate, representing less than five percent of the animal’s total body mass. It was affixed to its head via a skull adapter plate, which allowed for the device to be attached and removed at will. Imaging on the rodent’s brain surface was then performed with the microscope through a minimally-invasive, surgically-implanted cranial glass window.
Sigal and his colleagues were able to successfully record the brain during seizures, measuring blood flow and metabolism without anesthetic disruption over a period of six weeks. Their design and methodology was summarized in a paper entitled, “Imaging brain activity during seizures in freely behaving rats using a miniature multi-modal imaging system,” and was published on August 22, 2016 in the journal Biomedical Optics Express. Read it here.
With files from the University of Toronto.
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