A repurposed drug could be the key to successful stem cell transplants

by • December 20, 2017 • Feature Slider, Feature-Home, Featured-Slides-Home, Science Focus, Stem cellsComments Off on A repurposed drug could be the key to successful stem cell transplants576

Peter Zandstra. Credit: Paul Joseph/University of British Columbia

Canada is known for its long track record of success in stem cells, specifically in blood stem cells, and today will be no exception. Peter Zandstra, a founder and chief scientific officer at the Centre for Commercialization of Regenerative Medicine (CCRM) and director of UBC’s new School of Biomedical Engineering, as well as researchers from UofT and UBC, publish in Science Translation Medicine today, December 20, 2017, a potential way to repurpose an anti-inflammatory drug for blood stem cell transplants.

Earlier work looked at cell interaction and signaling between cell population where the researchers noticed that one of the growth factors tumour-necrosis-factor-alpha (TNF-a) – a protein that cells deploy against infection, which is sometimes overproduced, killing healthy cells – had a negative effect on blood stem cells. This observation emerged when the researchers did not get the expected number of stem cells to rise to mature blood cells during blood stem cell transplantation. This finding influenced Zandstra to explore whether one of several existing drugs that block TNF-a would allow human blood cells to thrive in a new host.

“If this strategy boosts the survival rate of blood stem cells in humans, then we can get away with using smaller grafts,” says Zandstra. “That would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible – not only for blood cancers, which we are already doing but also for auto-immune diseases, like Crohn’s disease, even HIV.”

Zandstra and his team added the blocking agent either with the transplant or up to two weeks later. The results they received from testing on animal models far surpassed expectations. The mice had numerous more blood stem cells, and more importantly, diversification – more rapid T and white blood cells, which suggested a healthy transplant.

“You never know when you take things in vivo and into animal situations,” comments Zandstra. “We knew from our experimentations and our mathematical modeling that we should have a positive effect, so we are quite pleased when these predictions turned out to be true. I think from a clinical perspective, one of the things that is very exciting about this is that it could be fairly rapidly translated to human patients. The drug is already approved and people are already doing blood stem cell transplantation, so overlaying this as part of a therapy could be an exciting way to go.”

Smaller grafts will provide two main benefits. The first being that there are many of those available with a large pool from which to choose; and second, the potential to have better matches from those existing pools. A significant portion of banked umbilical cord blood is simply not suitable for use on adults because they are either too small or not appropriately matched.

“I think what we’re starting to see in stem cell transplantation, certainly in blood stem cells, is that we are moving to more sophisticated therapies that have significant benefits to patients. Already it’s a therapy for some types of leukemia and other diseases. We are seeing gene-edited T-cell therapies (CAR-T) in a number of cancers, and it’s just going to increase further as we gain confidence in our ability to engineer the environment for the cells in a transplant and have this effect.”

These results provide a strong basis to advance the research to clinical trial and observe whether TNF-a blockers improve patient outcomes or save lives. This repurposed drug could be the key to successful stem cell transplants.

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