BIV Magazines: LifeSciences 2008

A major scientific breakthrough sees adults stem cells transformed into a more “primitive” state – reducing the need for a donor transplant and the risk that the new cells will fail

By J.K. Malmgren

The spotlight on regenerative medicine – and specifically stem cell research – is beaming brighter everywhere but perhaps nowhere more so than in B.C.

According to a recently prepared asset map of regenerative and stem cells issued by the provincial government, more than $178.6 million covering 962 projects and awards was spent on regenerative medicine research between 2001/2 and 2005/6. Of that sum, $67.5 million was invested in stem and mature cell research. And B.C. inventions have formed the basis for 50% of the province’s 18 regenerative medicine companies, helping make B.C.’s regenerative research sector among the most mature in the world.

Dr Allen Eaves, a physician-scientist, became the founding director of the Terry Fox Laboratory at the BC Cancer Agency in the early 1980s. He was joined by his wife, Dr. Connie Eaves, and their seminal work led to many of the early discoveries that today underpin the field of stem cell biology and its fledging application to the treatment of diseases such as cancer and transplantation.

Stem cells have the ability to continually reproduce themselves while maintaining the capacity to give rise to other more specialized types of cells. They play a critical role in developing and maintaining the human body. And they seem to have an endless potential to change the way we treat generative diseases and even injuries that range from almost any form of cancer to diabetes to severe spinal cord trauma.

“Cellular therapy is where we take healthy stem cells and insert them into patients, instead of drugs,” said Allan Eaves. “This can be done by taking the patient’s own cells, treating them and putting them back in, or by transplants. And anything you can conceive is probably possible.”

Although ostensibly retired, Eaves continues his research at the laboratory, focusing on chronic myeloid leukemia and the opportunities for stem cell therapy to contain and overcome that disease.

“It’s stem cells that go wrong and grow out of control that cause leukemia. One of the ways to treat that is to get rid of all those cells, and then replace them with tissue matched donors.”

That means a bone marrow transplant, usually from a brother or a sister. But even with a relative that close, the chance of an acceptable match is only one in four. And the eradication process, which means radiation therapy, comes loaded with pitfalls. “Leukemia stem cells exhibit a ‘genetic looseness.’ They can adapt to the chemo poison very quickly.” So they may begin to resist those eradication efforts before a successful transplant can be made. If the chemotherapy process is successful, it takes out all of the patient’s leukemia stem cells, healthy and otherwise, leaving an extremely vulnerable recovery period.

Part of Dr. Eaves’ research is looking for ways to avoid the need for transplant therapy at all.

“When you treat leukemia without a transplant, you’re trying to use drugs that will kill the leukemic stem cells and spare the normal ones. We’re learning to better understand the leukemic stem cells so we can better target the chemotherapy to them.”

A large part of the research has been the development of in vitro and animal model systems that become the basis for the studies. These, in part, have led Eaves to form two companies, StemCell Technologies and StemSoft Software. “I know what is needed – high-quality products that give reproducible results. You have to know that your media won’t be a problem.”

That is the primary focus of StemCell, which markets tissue culture media for growing different types of stem cells and products that allow the separation of cells. StemSoft develops software to support the cellular therapy sector with solutions for information management, quality assurance and regulatory compliance requirements.

Perhaps the greatest leap to date in stem cell research has come about a little unexpectedly. The reason embryonic stem cells are highly valued is that they are primitive – undifferentiated and therefore able to be utilized in almost any way. The same is true of cells taken from umbilical cord area blood, but the cost of extraction and preservation is high, and amounts are so small that it would take two or more extractions to accommodate an adult bone marrow transplant. Adult stem cells need to be transplanted very specifically from organ to organ, and with much more care taken to make an exact match. But the development late last year of a new technology that creates induced pluripotent stem (IPS) cells that share many physical, growth and genetic features of embryonic stem cells may yet overcome those hurdles.

“What this process does is de-differentiation – taking the cells back to a more primitive state,” described Eaves of the process that can start with adult skin cells. “If you can take a mature cell and get it back to a stem cell state, you don’t need to store core blood cells. And if you can use the patient’s own cells, with no concern about rejection, it will be wonderful.”

The process has by no means been perfected. But Eaves sees tremendous cause for optimism, and points to it as an example of the strength of the research community and the way advancements sometimes come about.

“Making these IPS cells was totally unanticipated and, in 100 years, everyone may have IPS cells safely stored to keep them healthy.”

In what is a quantum scientific leap, B.C. seems set to capitalize. In all, 80 companies have signed at least 141 contracts or agreements worth almost $23 million with B.C.’s regenerative medicine researchers over the past five years – among them eight of the world’s top 10 pharmaceutical companies. With a new and potentially unlimited source for the stem cells themselves, those sectors look set to prosper further. •

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