« September 2010 | Main | November 2010 »

9 posts from October 2010

October 22, 2010

Questions raised about XCell Center

This post has moved!

Please read it on its new home, Signals BlogQuestions raised about XCell Center

October 21, 2010

Till and McCulloch inducted into Science and Engineering Hall of Fame

This content has moved!

Please check it out on its new home, Signals BlogTill and McCulloch inducted into Science and Engineering Hall of Fame

October 19, 2010

The tell-tale heart: Firefly genes for stem cell tracking

by Chris Kamel

As mentioned in a previous post, in order to fully understand what's happening when stem cells are used for in clinical or in vivo research, we need some way to track them, preferably in a non-invasive manner. This can be done with either reporter genes or some sort of traceable label, and would allow researchers to watch the cells as they migrate and differentiate in the body or research animal. Using luciferase, the protein that makes fireflies glow, researchers have been able to non-invasively image cardiac stem cells in a living mouse, according to research published in Stem Cells and Development.

In the study, researchers generated mouse ES cells expressing luciferase under the control of a cardiac-specific promoter (Ncx-1). Under these conditions, the stem cells appear normal until they differentiate into heart cells. When heart genes are expressed (specifically Ncx-1), these cells will turn on the firefly luciferase, which can be made to glow, allowing tracking of the cells.

The researchers first demonstrated this in vitro, showing that only ES cells that differentiated into cardiac cells had bioluminescence. When injected into the heart, the cells were seen in the chest cavity of mice as early as four days, persisting for as many as 24 days. The cells were able to align with existing tissue and maintain a cardiac muscle phenotype.

This work was done with otherwise healthy, newborn mice, but the authors hope to use this method to see how stem cells behave in adult mouse models of heart disease. This system provides a non-invasive way to monitor stem cells in individual live animals, allowing scientists to track their migration and differentiation when designing new protocols and testing them in pre-clinical studies. Ultimately, it could be used as a way to follow patient progress without the need for surgery. This method could even be adapted for use in other organs by using different tissue-specific promoters.

Another interesting finding was that the procedure worked better when the number of cells injected was lower, and when differentiation was initiated before injection. With a high number of undifferentiated cells, many remained undifferentiated and spread outside the cardiac region into lung and other tissue. At a moderate dose, the cells were more localized to the heart. Triggering differentiation before implantation improved the formation of heart tissue while reducing the chances of tumour formation. This kind of information about dosing and safety is only available through pre-clinical and clinical trials, such as the current Geron stem cell trial that recently treated its first patient, and mark the difference between legitimate therapies and those offered by less scrupulous "clinics" that offer untested "cures" to the hopeful and desperate.

October 18, 2010

Stem Cell Network honoured with 2010 Stem Cell Action Education Award

by Drew Lyall

Earlier this month, the Stem Cell Network was delighted to be honoured at the World Stem Cell Summit in Detroit with the 2010 Stem Cell Action Education Award. Presented by the Genetics Policy Institute (GPI), the leading stem cell advocacy organization in the United States, the award recognized "the Network's extraordinary commitment to public education". Previous winners have included the National Association of Biology Teachers (2008) and the Michigan Citizens for Stem Cell Research and Cures (2009).

While the Network, it researchers, and its students undertake literally hundreds of outreach events and activities every year, GPI highlighted four programs in particular:

  1. StemCellTalks, a high school outreach program led by three graduate students at the University of Toronto, that is being rolled out across Canada in 2011;
  2. StemCellSchool, a recently-launched web-based resource aimed at high school biology students that teaches basic biology concepts through the "lens" of stem cell research;
  3. SCN Ethics Whitepapers, a series that summarizes many of the ethical, legal and social questions that arise from stem cell research, in a form that is accessible to the general reader; and,
  4. SCN Patient Summaries, both a web-based and hard-copy resource that aims to summarize the latest information about the potential application of stem cell research to various disease areas, in a form that patients can readily understand.

As one of Canada's Networks of Centres of Excellence, public outreach, education, and engagement are central parts of our mandate, and ones into which we have invested heavily over the past decade. Nevertheless, it is always nice to receive external validation of the work being done though none of it is done alone - credit must also be given to the many trainees and PIs who volunteered their time to the projects, as well as to the members of the Network's Policy Development Committee and to Lisa Willemse, our Director of Communications, who manages these programs.

October 14, 2010

RNA-induction: A new method for iPS cell production

This content has moved!

Please read it on its new home, Signals BlogRNA-induction: A new method for iPS cell production

October 08, 2010

Stem cells and high throughput screening

By Allison Van Winkle

High-throughput screening, in which many cell culture conditions can be tested using a combination of robotics, control software, and/or highly sensitive detection, allows researchers to explore new ideas quickly; thousands of combinations can be efficiently tested for toxicity, cell viability, proliferation or differentiation. 

Recently, high throughput screening was used to search a library of over a thousand small molecule compounds, to find promoters and inhibitors of mesenchymal osteogenic differentiation. This differentiation process is of great interest to regenerative medicine researchers, as osteogenic (bone material) cells could be transplanted into patients suffering from osteoporosis, or other degenerative musculoskeletal diseases. This approach could be used for any stem cell type and differentiation lineage; where a differentiation characteristic is identified and tested, and statistics are used to compare each test with a positive and negative control. Once the field is narrowed down to those which show the most promising results, larger scale experiments can further quantify the cellular response and point to avenues of further study or clinical trial. 

High throughput screening is also commonly used to test new drugs or therapies. Compounds which target the cells responsible for neuroblastoma tumours were identified with a small molecule screen, which led to therapeutic candidates to focus further research on and a Phase 1 clinical trial. Similarly, high throughput screens could be used to test drug toxicity much earlier than the status quo for clinical trials, or possibly even develop a scheme for personalized drug testing, using induced pluripotent stem cells derived from a patient’s own cells. 

As bioengineering advances and new high throughput screening procedures are developed, the process may become more automated. This allows for even more conditions to be tested, and the future of stem cell research, whether it is the development of drugs and therapies, or stem cell differentiation protocols, remains promising. 

October 06, 2010

Special delivery: Getting stem cells into the spinal cord

By Katie Moisse

Day two of the World Stem Cell Summit featured a much-anticipated update on a groundbreaking clinical trial launched in January to assess the safety and feasibility of injecting fetal stem cells into the spinal cords of people with Amyotrophic Lateral Sclerosis (ALS).

To describe injecting a million cells into the precise area of the spinal cord that is home to the motor neurons degenerating in people with ALS as “tricky” would be somewhat of an understatement. For starters, the spinal cord is buried in a thick, boney spinal column tucked under layers of muscle. And just when you think it’s uncovered, a tough, blood vessel-laden membrane called the dura makes one final, stingy stand.

Nevertheless, in ten months neurosurgeon Nicholas Boulis from Emory University in Atlanta has delivered millions of spinal cord-derived fetal stem cells (supplied by Neuralstem Inc., an American biotechnology company) into the spinal cords of six ALS patients no longer able to walk because of their disease. Boulis uses a special “stabilized microinjection platform” for precision to target the injection to an area smaller than a grain of rice called the ventral horn. Three patients have received the cells on only one side of the spinal cord (so the other side can serve as a control), and another three have received bilateral injections.

Now Boulis and colleagues Eva Feldman from the University of Michigan and Jonathan Glass from Emory University (co-principle investigators for the trial) are recruiting ALS patients who can still walk, with the hopes that, when initiated early, cellular therapies will ultimately help preserve motor neuron function and delay disease progression.

“We began this trial with those who had severe disability and thus were at a lower risk for added weakness that may occur as a consequence of stem cell injection into the spinal cord,” the team wrote in a trial update posted on their web site. “We are now moving forward with patients with less disability.”

Their early concerns weren’t unwarranted. Like all experimental treatments, this one carries risks (including surgical ones) and the potential for serious side effects. There is evidence that injecting anything into the central nervous system can provoke inflammation, which in ALS is thought by some to accelerate disease progression. And certainly the risk of an immune response is heightened when the injectable contains cells that aren’t the patient’s own. However, the patients are reported to be doing well.

While the injected cells are capable of becoming motor neurons, it’s unlikely that’s how they might confer a benefit. To do so, they would have to project axons up to a metre long connecting to specific muscles. Rather, the cells might act as growth factor-spewing “biological minipumps” or as mops that “sop up excitatory amino acids like glutamate,” according to Colin Franz from the University of Calgary, who was involved with the trial at Emory.

But whatever the mechanism of action, finding a way to get stem cells into the spinal cord of vulnerable patients without causing more harm is an important and ambitious first step towards cellular therapies for people with ALS.

October 04, 2010

Fireside chat with Jim Till and Janet Rossant

This content has moved!

Please check it out on its new home, Signals BlogFireside chat with Jim Till and Janet Rossant

October 01, 2010

Is 2010 the year of the stem cell Nobel?

For the second year running, mainstream media in Canada and abroad has picked up on Nobel buzz surrounding stem cell scientists James Till and Ernest McCulloch, both Senior Scientists at the Ontario Cancer Institute in Toronto. Speculation surrounding a Nobel prize can be traced back to 2005, when the pair were awarded the Lasker Prize, often touted as America's Nobel and viewed as a predictor of future Nobel success.

The particular interest generated in the past two years have been based largely on annual predictions from media giant Thomson Reuters. Reuters has been predicting Nobel Laureates in chemistry, medicine, economics and physics since 2002 using citation data, and while their predictions have not always been accurate - the Nobel Assembly keeps their nominees list under tight wraps - they have correctly identified 19 Laureates using their citation methodology.

So, is this the year for Till and McCulloch? From the standpoint of science, they are eminently deserving of the prize - the groundbreaking work they did in the early 1960s formed the basis of life-saving therapies that have been used to treat thousands of patients with leukemia and other blood disorders, and has defined an entire lexicon and understanding from which the entire field of stem cell science has been built.

Oddly enough, the prize could be seen as being even more important in terms of building awareness and pride in Canada. The fact that two brilliant researchers, who have contributed so much to our current understanding of medicine and disease, are largely unknown in mainstream society is shameful. Till and McCulloch should be on the list of every top 10 influential Canadians. School children should be learning about their discovery and finding inspiration in their methods. Yes, we should be waving the Till and McCulloch flag. But we're not. At least not yet.

Maybe this will all change on Monday. It couldn't happen to two better Canadians.

- Lisa Willemse