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10 posts from December 2010

December 29, 2010

New regenerative medicine centre announced by Canadian government

Earlier this month, the Honourable Tony Clement, Minister of Industry, announced the establishment of the Centre for the Commercialization of Regenerative Medicine (CCRM) with a $15 million initial investment. The CCRM will be based in Toronto and is one of five new CECR’s funded through the Networks of Centres of Excellence program.

While stem cell research continues to make rapid progress and we are now seeing initial transition into the clinic, in relative terms the regenerative medicine industry is still in its infancy. This new Centre seeks to focus energy and resources into leveraging Canada’s research investment into a commercial presence in three emerging technology platforms that will be crucial to the long-term development of a Canadian regenerative medicine industry.

The closer cell based therapies get to the clinic, the more obvious and urgent become the more practical manufacturing and bioengineering issues relevant to delivering cells at scale to patients. Cell isolation and purity, expansion while maintaining function, batch-to-batch potency, and cryopreservation are critical issues that remain to be addressed. Systematic and repeatable manufacturing solutions need to be developed in partnership with industry. Consistent and repeatable delivery of cells at scale, especially cardiomyocytes and hepatocytes, is also being called for by the pharmaceutical industry to enable enhanced predictive toxicology testing, and screening for new drug targets. As a result, CCRM’s initiative to develop new technologies to enable and support GMP cell manufacturing facility will yield many practical clinical and commercial applications over the next five years.

Continue reading "New regenerative medicine centre announced by Canadian government" »

December 21, 2010

StemCellTalks Vancouver delivers

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Ben Paylor introducing speakers at StemCellTalks

by Ben Paylor, Maisam Makarem and Véronique Lecault

December 3rd, 2010. 8:45am. The auditorium lights of the Michael Smith Laboratories at UBC dimmed on nearly 50 eager Greater Vancouver high school students and 15 volunteers. The mood was one of excitement and nervousness, although some had an idea about what the day would hold, nobody really knew for sure. Following the ever-relevant Stem Cell Charter video, the lights came on and the first satellite StemCellTalks symposium in Vancouver began.

First on the podium was a local bone-marrow transplant expert, Dr. Kai Luecke, interviewing a patient who had benefited from stem cell transplantation after being diagnosed with acute myeloid leukemia. Together, they guided us through a moving story from initial diagnosis, to therapy and eventual recovery. It was the perfect start to the day as it gave the students a firsthand clinical perspective on how stem cells are currently used today.

Continue reading "StemCellTalks Vancouver delivers" »

December 20, 2010

The buzz about innovation

by Paul Krzyzanowski

Basic scientific research is a fundamental driver of improved quality of life that our society enjoys. However, it's tacitly acknowledged that the benefits of research sometimes don't materialize until some time has passed, with the finish line sometimes decades away. This length of time for an advance to be recognized as 'valuable' is extremely unpredictable -- so much so that it's one of the major points of dispute between those who conduct research for knowledge's sake and those eager to see the benefits of the research put into practices.  

Scientific advances and newly discovered techniques are always shared and copied by researchers, most of whom appreciate the time and skill required to learn how to do so. It's not always easy to replicate what someone else has done in another lab, even for someone considered to be a specialist in a subject area.

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Trending topics in hematology: summary of the 2010 American Society of Hematology conference

by Michelle Ly

Stem cells were high on the list of hot topics at this year's American Society of Hematology conference in Orlando, Florida, particularly regarding the uses and effects of stem cells in the treatment of disease.

The Ham-Wasserman lecture, named for two past ASH presidents, was presented by Tsvee Lapidot, from the Weizmann Institute in Rehovot, Israel. His lecture looked at stem cell homing and mobilization, and will be the topic of an upcoming post. Harvard University’s Leonard I. Zon presented “Blood Stem Cell Self-Renewal and Differentiation – Lessons from Embryonic Development” as the part of the E. Donnall Thomas Lecture and Prize series. Dr. Zon discussed the use of zebrafish as a model for examining the pathways of hematopoietic stem cell formation. His work has demonstrated that signaling pathways, which are crucial for initial blood stem cell development, are also involved in adult stem cell renewal.

Several interesting studies were presented during the press conference on the role of stem cell transplants in the treatment of blood cancers. Alexander H. Schmidt of the DKMS German Bone Marrow Donor Center conducted a retrospective study of over 12,000 unrelated donors of peripheral blood stem cells and bone marrow and found that this group did not have an increased risk of cancer. This was a concern raised previously in literature due to the use of filgrastim and similar drugs to mobilize the stem cells to the bloodstream. In the realm of patient treatment options, Amrita Krishnan, director of the Multiple Myeloma Program at the City of Hope Cancer Center in Duarte, California, compared autologous versus allogenic stem cell transplantation for patients with standard risk multiple myloma.

His study team found that the choice of tandem autologous stem cell transplant versus autologous transplant followed by an allogenic transplant did not affect overall outcomes or survival.

Indeed, these were only the tip of the iceberg. Over the two-day poster session, many more abstracts were presented on this topic, perhaps indicative of the strong, growing role of stem cell transplantation in healthcare. The efficacy of cell therapy, the use of cord blood, the choice of allogenic versus autologous transplant, and availability of new experimental treatments in the areas of leukemias and myelomas were among the many topics presented during the informal poster sessions. But while the focus was definitely on clinical results and applications, a number of abstracts also looked at the biology of hematopoietic stem cells, studying aspects of the stem cell micro-environmentregulation and development.

Finally, as the weekend wrapped up, ASH also honoured David T. Scadden from the Harvard Stem Cell Institute with the William Dameshek Prize, in recognition for his achievements in stem cell mobilization and imaging.

December 16, 2010

US report sets out basic ethical principles for assessing emerging technologies

by Ubaka Ogbogu

President Obama’s Commission on the Study of Bioethical Issues today released a report of its ethical investigation and recommendations for oversight of the emerging field of synthetic biology. The report responds to a charge to the Commission issued by the President in May following the announcement by the J. Craig Venter Institute of the creation of the first synthetic organism. The report outlines eighteen key recommendations, which are neatly summarized in the following excerpts (annotations are mine):

On the hyped portrayal of the achievement as “creating life” and reliance on scientific evidence in policy deliberations

“The announcement last May, although extraordinary in many ways, does not amount to creating life as either a scientific or a moral matter. The scientific evidence before the Commission showed that the research relied on an existing natural host… The feat…does not constitute the creation of life, the likelihood of which still remains remote for the foreseeable future…The Commission therefore focused on the measures needed to assure the public that these efforts proceed with appropriate attention to social, environmental, and ethical risks.”

On proactive oversight of emerging technologies:

“We are ahead of the emerging science, and this unique opportunity underscores the need for the government to act now to ensure a regular, ongoing process of review as the science develops. The Commission calls on the government to make its efforts transparent, to monitor risks, to support (through a peer-review process) the most publicly beneficial research, and to educate and engage with the public as this field progresses.”

What I found most interesting about the report is the Commission’s take on the basic ethical principles for assessing emerging technologies. The report lists and discusses the following five guiding principles: 

  • Public beneficence: the government’s duty to promote scientific and biomedical research that “have great potential to improve the public’s well-being.”
  • Responsible stewardship: shared obligation to protect the interests of those who cannot represent themselves.
  • Intellectual freedom, backed by regulatory parsimony: proper oversight that balances public good with “justice, fairness, security and safety.” 
  • Democratic deliberation: “collaborative decision making that embraces respectful debate of opposing views and active participation by citizens.”
  • Justice and Fairness: fair and equal distribution of benefits and burdens.

As far as I know, this is the first time that the first four principles are being articulated and applied to biotechnology research at the policy level. This, in my opinion, signals a shift towards a more inclusive ethics, one that properly considers the ethically responsible interests of all—research participants, society, researchers, regulators—participating in and affected by the biotechnology research enterprise. It may be worthwhile for ELSI (ethical, legal and social issues) scholars to spend some time unpacking what these principles mean for biotechnology in general, and stem cell research in particular. 


How will chemically induced pluripotent stem cells impact stem cell policy?

by Ubaka Ogbogu

Chris Kamel’s recent post on chemically derived transcription factors for iPS cell production is very exciting for a variety of non-scientific reasons. Most notably, the innovative procedure and future improvements are likely to ease ethical, safety and legal concerns regarding the use of oncogenic transcription factors. One such concern is the possibility that Canadian law currently prohibits the further differentiation of iPS cells (derived from gene inducement) into germ cells (this is a logical next step in iPS cell research). The ban is mostly likely ‘collateral damage’ from definitional ambiguities inherent in the sweeping and confusing language of Canadian legislation on assisted human reproduction and related research. iPS cells had not been discovered at the time the legislation was enacted, and was neither contemplated nor mentioned throughout the legislative activity surrounding the law. The ban also depends on the interpretation that the genetic reprogramming method creates an inheritable alteration in the DNA of an iPS cell that can theoretically be transmitted to offspring if the iPS cell is differentiated into germ cells. If the germ cells so produced were then used for reproductive purposes, this, in the eye of the law, would amount to germ-line genetic alteration, an activity that is criminally prohibited in Canada. A law simply prohibiting the use of genetically altered germ-line cells for reproduction would not be objectionable (this is the case in Australia) but Canadian law appears to prohibit the activity for all intents and purposes. 

As predicted a couple of years ago by Peter Rugg-Gunn and I in a Journal of International Biotechnology Law piece on “The legal status of novel stem cell technologies in Canada”, the possibility that iPS cell differentiation into germ cells is banned in Canada “may be avoided with future refinements to iPS cell generation, for example by using chemical modifications to stimulate reprogramming without changes to the genome of the somatic cell.” It appears as if the latest research reported here is one right step in this direction. What would be best for this promising area of research are advances that sidestep possible ethical and legal controversy, and progress that stimulates and informs clear and responsible science policy. Kudos to the Scripps Research Institute team!

 

December 14, 2010

The business of scientific research

by Paul Krzyzanowski

One of the biggest choices graduate students and post-doctoral fellow face is whether to stay in academia or go into the business world.  

But what if the two weren't really that different?

Traditional advice about running a successful academic research group focuses on the development the Principal Investigator. A recent article by David A. Stone in The Chronicle of Higher Education splits the role of a PI into three: the scholar, the researcher, and the grant writer. The scholar generates and identifies good ideas to pursue and how to place them in well published papers, the researcher actually manages to get the work done, and the grant writer sells the potential of future research projects to funding agencies and foundations.

Continue reading "The business of scientific research" »

December 09, 2010

Chemically induced pluripotent stem cells

by Chris Kamel

Induced pluripotent stem (iPS) cells are generally created by the expression of a small number of key genes to reprogram adult cells into an undifferentiated, pluripotent state. Because some of the transcription factors used for reprogramming are oncogenes, as well as concerns about mutagenesis due to genomic integration, scientists have been searching for improved methods to create iPS cells. This includes new delivery methods for the required transcription factors and skipping the iPS step altogether by direct intercoversion of cell types. Recently, in a paper published in Cell Stem Cell, scientists at the Scripps Research Institute in California have found a way to create iPS cells using mainly a cocktail of drugs.

Building on previous work done with fully differentiated skin cells (keratinocytes), the authors began with chemicals known to improve reprogramming efficiency, eventually screening several compounds and reducing the number of exogenous genes required. Ultimately, they were able to produce a stem-like cell introducing only the stem cell marker Oct4 and a combination of four drugs. This feat was also accomplished in two other cell types. The resulting cells expressed a number of pluripotency markers and were able to differentiate into cells from all three primary tissue layers, a key sign of "stemness", and could be differentiated into a specific cell fate, in this case cardiac muscle cells.

Reducing the need for genetic manipulation is one goal of iPS research. With three of the four required genes now replaced with chemical compounds, we are now one step away from removal of Oct4 and the induction of stem cells using only small molecules. With that accomplished, these drugs can be further characterized and refined, offering new insights into the underlying biology of stem cell reprogramming and offering an efficient, reliable way to produce iPS cells while minimizing associated risks.

December 07, 2010

What’s next for stem cell biology: Royal Society Meeting October 2010

by David Kent

My last post was mostly centred on the lack of openness displayed by a growing number of scientists, but failed to comment on the wonderful array of findings that were presented by world leaders in stem cell biology. The Royal Society Meeting that took place in October was definitely designed “for scientists” and the juggernauts came out in full force.  

The meeting started off with an excellent talk from Kazutoshi Takahasi in which he described a gene that looks to be able to distinguish induced pluripotent stem cells that are prone to developing tumours in mice from those that are not. This could be a massive advance for an emerging field that faces some serious questions about the safety of future therapeutics.  Sadly, the gene name was not given to the audience.

One of the most driven scientists I have encountered in my short time in research is Doug Melton, who after making seminal contributions to the field of reprogramming via nuclear transfer, completely switched his lab over to studying juvenile diabetes upon learning that his own child had the condition.  A great article on Doug Melton was written in 2005 that charts his journey. The pace at which the Melton lab has moved the juvenile diabetes field is remarkable. He has focused much attention on deriving insulin secreting beta cells from both ES and iPS cells and updated on this progress at the meeting. While researching a little for this article, I stumbled on a presentation not dissimilar from the one Dr. Melton gave at the meeting, which is a good overview of the process: it shows how chemicals added to ES/iPS cultures can help drive primitive cells to produce beta cells.

The final afternoon session began with a story that I first heard at the ISSCR meeting this past June, but definitely deserves mentioning again as it has become one of the hottest areas in cell biology.  Marius Wernig presented his group’s work on directly reprogramming skin cells into neural cells using a very similar approach to that of the Yamanaka group for iPS cells –- using neural cell transcription factors instead of pluripotency transcription factors.  The next few years are bound to be full of similar reports (e.g.: blood cells from skin cells) from the various tissue types as the reprogramming field continues to grow.

Directly following this talk was a sobering dose of reality from East of England Stem Cell Network Director Cathy Prescott, who spoke about the “business of iPS cells” and laid out a very convincing set of numbers showing that patient-specific iPS cells carry little to no ability to attract private sector investment due to high costs associated with patient-specific development and the lack of a commercializable product. 

Overall, the Royal Society put together a fantastic set of speakers and it was a real pleasure to attend (for free no less!). However, it makes me wonder: the British Royal Society academic meetings can attract prominent scientists from across the pond -- could it's Canadian counterpart organize an event with similar scope?   


December 01, 2010

And the winner is...

Of all the projects we run out of our small admin office, certainly one of the more visually compelling is the Cells I See art contest. As a side event at the Network's scientific meeting, Cells I See usually elicits a great deal of buzz, as conference attendees speculate on what might be the winning entry. It's not unlike the lead-up to the Oscars, albeit on a much smaller scale -- and without the red carpet. How so? Well, an active campaign might just sway the vote.  

We all know that contenders for best film and director prizes at the Oscars spend a great deal of time and money trying to woo the Academy into tossing a statuette in their direction. How well that works is up for debate, but it makes one wonder about some of the winners over the years. Now, before anyone assumes that the winning Cells I See entries are perhaps not deserving of their award, let me assure you that this is not the case. While we have not always been able to predict the winners, they have always been among the best of the entries received. The point is, that, in at least two of the three years we've run the Cells I See contest, the winning entry has been the subject of a rather intense amount of campaigning by its supporters. Whether the campaigns have been enough to sway the outcome of the contest is anybody's guess. But it does make for some great entertainment at the conference. 

In the absence of our scientific meeting next year, we know there will be changes to the contest for 2011. Hopefully the fun of a good campaign will not be among them.

So, hearty congratulations to this year's winner, Kamal Garcha of the University of Toronto for his entry, "The Beauty of Pluripotency". Thanks to all those who entered - the entries this year were exceptional - and also to our Cells I See sponsor, Fate Therapeutics.

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 Kamal Garcha - The Beauty of Pluripotency

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Erika Murray - Pancreas Pisces

Aarts_Sphere-ologySM 
Craig Aarts - Sphere-ology 

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Marta Szabat - Life Stages of a Beta Cell

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Peter Tonge - All for one and one for all