McMaster University

Kristin Hope of McMaster University’s Department of Biochemistry and Biomedical Sciences. Photo credit: McMaster University 

Few physiological discoveries have achieved the popular profile awarded to stem cells, touted as biological superheroes with the power to replace diseased and damaged cells almost anywhere in the body. Most of this new field of medicine remains highly experimental, although some proven therapies have already emerged, particularly the use of blood stem cells to treat such difficult disorders as leukemia, lymphoma, aplastic anemia and sickle cell disease.

While stem cells get all the glory, the real heroes are their laboratory sidekicks who struggle constantly to grow and maintain ongoing lines of these finicky organisms for clinical use. The adventures of these unsung helpers are largely tales of frustration as they attempt to decipher the intricate chemical patterns that give stem cells their seemingly magical abilities. 

After more than 10 years in this field, Kristin Hope knows these tales only too well. The assistant professor in McMaster University’s Department of Biochemistry and Biomedical Sciences came to love stem cells after what she had seen them do for patients, even as the cells resisted her efforts to nurture their numbers. “We don’t know enough about what’s going on in those cells when we put them in the ex vivo environment,” she says. “When you put them in a culture dish, they behave very differently. The genes and proteins that they turn on and off are completely different. And that’s a problem when what you want to do is make buckets of these cells for regenerative purposes.”

Hope consequently devoted herself to identifying the key biomolecular players responsible for the way stem cells behave in the laboratory, as opposed to the human body. Among the most prominent of these players is a protein called Musashi-2; when it is absent from the cells, they no longer replicate themselves and when it is over-expressed they renew themselves at an unprecedented rate. 

This finding was recently published in Nature, where Hope and her co-authors point to Musashi-2 as a means of amplifying the available supply of blood stem cells. While these cells can be taken from bone marrow, matching a healthy donor’s cells to a patient can be difficult, especially in the case of some ethnic groups. Cells harvested from a newborn’s umbilical cord — which are uncomplicated to obtain — encounter far fewer problems interacting with a patient’s body. Unfortunately, any given cord will provide only a small number of cells, making it crucial to expand their number in a laboratory setting if clinicians are going to make any practical use of them.

“This over-expression of Musashi-2 overrides the problems that we have when we put these cells in a culture dish,” she says, noting that her next challenge­ consists in learning what drives this protein so that she can manipulate it for therapeutic purposes. Hope is already aware of some commercially available inhibitors, drugs that could affect a target molecule in ways that would make it possible to increase the available amount of Musashi-2 for production purposes. “I want to understand this system, understand the key players, then I can start to find things that impact those key players: small molecules and drugs.”