Sonic Hedgehog

Bone marrow transplants help save countless lives every year, but for donors the standard procedure can be painful: A syringe with a hollow needle is inserted into the hipbone to extract the marrow.

But, once transfused, stem cells in that donor marrow can produce new blood cells to replace those damaged by chemotherapy or radiation.

Now, a team led by a renowned Canadian stem cell biologist has discovered that a protein can be used to multiply a few blood stem cells into potentially millions – a finding that could make the life-giving procedure easier on donors and recipients.

In the future, the molecule could be used to increase the number of stem cells collected from a cancer patient’s own blood before undergoing treatment. Then, the cells could be transplanted back into the patient to repair his or her damaged blood-forming systems.

The protein is called Sonic Hedgehog. What has researchers the world over excited is the spiky molecule’s ability to manipulate blood stem cells into reproducing, without losing their “stemness” – that is, their ability to develop into all other blood cells.

“Unlike what’s classically used clinically, our results suggest that these molecules play a far more substantial role in increasing stem cell numbers,” says Dr. Mick Bhatia, principal scientist at the Robarts Research Institute in London, Ontario, and senior author of a study on the finding published last year in the prestigious science journal, Nature Immunology.

Until now, researchers trying different combinations of growth factors to make stem cells grow have all come up against the same wall: not only do the stem cells proliferate, they differentiate, and therefore lose their stem cell properties. That means that their progeny or “daughter cells” are no longer capable of making different kinds of cells, or making more of themselves. Instead, they have grown into a specific cell with a specific function.

“The problem is when you culture human stem cells, the cells lose their stem cell properties, resulting in an overall loss of stem cells. We believe the conditions used to culture these stem cells alter stem cell properties, and differentiate the cells,” says Dr. Bhatia, a member of the Stem Cell Network, a national research network based out of the University of Ottawa. Instead of simply “tweaking” the concentration and combinations of known growth factors classically used, Dr. Bhatia’s team is using a whole new set of proteins normally found in higher amounts during early human blood development.

“We know where hematopoietic stem cells came from, and we all have more than one. So there must have been a point during our development, probably in utero, when there must have been a rich source of factors to expand that stock of this pool of cells. This expansion is exactly what we hope to mimic in our culture systems using adult stem cells.

“We’re actually going back to those factors and saying, ‘what’s happening at that early stage of development, which genes are being expressed’, so that we can now present that to the adult version of our stem cell, and essentially re-program it to begin to grow like it once did.”

Dr. Bhatia is also looking at whether sonic hedgehog proteins could be used to grow neural stem cells, research that could one day lead to stem-cell based therapies for Parkinson’s and other neural degenerative diseases.

The 32-year-old scientist has fast emerged as one of the world leaders in stem cell research. This year he was named one of Canada’s “Top 40 Under 40” by Report on Business magazine. Since 1994, he has published 29 papers, many of which appeared in some of the world’s leading science journals, on his work to unravel the mysteries of stem cells.

Although he is focused on adult stem cells, Dr. Bhatia says research on embryonic stem cells must move forward too.

“The reality is you have to study both, because there is not enough data to conclude one is better than the other.

“I think it would be unethical not to continue with human embryonic stem cells. There is the potential to help people, and if we don’t start working on it, every day is one day lost.”