HEMATOLOGY
A Fantastic Voyage continued
out . It gets a Swiss cheese conformation and the rate at which we can dissolve the clot is much faster .”
A PRODUCT OF COLLABORATION
So far , this technology has only been tested in animal models , but the results are promising . Neeves and his team have decreased clotbusting time using a combination of microwheels and thrombolytic therapy by a factor of 50 over thrombolytic therapy alone .
This outcome , Neeves says , is the product of dozens of people in a variety of fields coming together in one cohesive space to solve a pressing , though underappreciated , problem . This collaboration is only possible at places like the Anschutz Medical Campus , which , in addition to housing Children ’ s Colorado , also includes the University of Colorado School of Medicine .
“ Being on this campus , being able to leverage the different facilities we have , and just the human capital is unique ,” he says . “ There are only a handful of places in the country where you can do this kind of work .” •
KEITH NEEVES , PHD
Professor , Bioengineering and Pediatrics , Section of Hematology , Oncology and Bone Marrow Transplant , University of Colorado Denver
Neeves ’ microwheels are just one example of how his work contributes to the scientific understanding of blood disorders . Two additional projects have the potential to improve patient outcomes and make major waves .
Organ on a chip Mathematical models of clotting
When it comes to running new tests and experiments , most researchers rely on animal models . But a new scientific movement takes human-derived cells and grows important features of an organ in a lab . In Neeves ’ case , this means taking endothelial cells , which line human blood vessels , and growing them inside tubes the size of a human hair .
“ We can grow them inside of these little tubes and then apply different kinds of insults to them , run blood through them and watch clots form ,” Neeves says . “ You can see these clots forming at the cellular scale , which is hard to do inside of an animal or inside of a person . And then we have total control over everything .”
The goal of this work is to eventually achieve personalized medicine . One day Neeves hopes that he can recreate an individual patient ’ s exact situation through this process and test different treatments to determine the best option for them .
Working with applied mathematicians at Colorado School of Mines and University of Utah , Neeves has created mathematical models that allow him to run 100,000 clotting simulations in just a few minutes . Neeves says the idea is that if they can build strong mathematical models , they can use the information as a screening tool to better understand how the composition of someone ’ s blood might affect its ability to clot or not , particularly in the case of hemophilia .
“ You can think about it as having hundreds of knobs on a control panel and then randomly turning them all ,” Neeves explains . “ The model pulls out these key tweaks and says , ‘ If you turn this knob and this knob , then we get this really interesting and maybe counterintuitive result .’”
Using statistical methods , Neeves ’ team extracts the most interesting findings and uses experimental methods to verify them . The results go right back into the model , making it better and smarter over time . Most recently , this approach alerted Neeves ’ team to a possible novel modifier of bleeding in hemophilia . They validated that via experimentation and are now diving into whether that finding is a potential therapeutic target .
6 | CHILDREN ’ S HOSPITAL COLORADO