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8 posts from January 2011

January 27, 2011

Progress being made in developing stem cell-based treatments for ALS/MND

Earlier this week, many of the world’s leading scientists engaged in developing stem cell-based treatments for Amyotrophic Lateral Sclerosis (ALS) or Motor Neuron Disease (MND) met for the first time as a group to share their work. Held in New York, the meeting was organized by the International Consortium of Stem Cell Networks in partnership with the ALS Association and the Motor Neuron Disease Association. Researchers, physicians, surgeons and patient advocates from more than a dozen countries participated.

At present, there is no consensus on the etiology (i.e. the cause or origin) of ALS, and there is a recognition that the disease presents in many forms. Furthermore, while it is often thought of as a single disease, there is ongoing debate about whether it is a disease or a syndrome (a range of conditions). To patients, it doesn’t really matter:  today, diagnosis is a death sentence within three to five years, as the body slowly and painfully shuts down. But for science, this distinction is important, because understanding the cause will allow treatments that target the cause, rather than relieve the symptoms, to be developed.

Nevertheless, progress is being made. While differences abound on the cause of the disease there is more consensus to how stem cells can help to find the answer. The discovery of iPS cells has revolutionized the process of scientific discovery in this field. Many of the world’s leading ALS labs have formed an iPS consortium funded by the US National Institutes of Health, ALS Association and others to develop new stem cell lines from patients living with ALS. These lines are being used in two different ways: 

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January 26, 2011

Mind the gap: study examines newspaper coverage of stem cell tourism

by David W. Grant

Mindthegap How do newspaper articles portray stem cell tourism? 

A research team at the University of Alberta recently asked this question, and their results were published last month in the journal Nature. Their conclusions were both surprising, and hopeful.

The team, led by Timothy Caulfield, analyzed tonality, agenda setting and framing in 445 newspaper articles on stem cell tourism, dating from October 2006 to September 2009. The results: (1) newspaper articles portrayed stem cell tourism largely in a positive tone, and (2) this trend increased with time. In terms of content, (3) the articles were primarily about individual patients, their hopes and fears, and the specific treatment plans or its supposed scientific approach, rather than the potential risks associated with an unproven treatment or the current scientific limitations on which it is based, or the many clinical, economic, and policy questions about stem cell therapy that remain controversial and largely unanswered.

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January 24, 2011

Genetic diversity in leukemia cells

by Chris Kamel

Although tumours are typically thought of as a single entity, the cells that make up a tumour are genetically diverse. The traditional view of cancer progression -- in which a tumour arises from a single cell after accumulated mutations -- suggests that tumour cells, while genetically diverse due to selective pressures and other evolutionary forces, are all linearly related. Similarly, in the cancer stem cell model, tumour growth is driven by an underlying stem cell population and tumour cells would be genetically related. Work published this week in Nature challenges assumptions about the relationships between cells within a single tumour.

The work, done by Dr. John Dick's group at the Ontario Cancer Institute, used a leukemia model and a combination of tumour transplant and genetic profiling and found that cells taken from patients with acute lymphoblastic leukemia are actually derived from multiple distinct families. Tracing the the ancestry of these cells, they found that rather than a linear evolutionary succession, the profiles indicated a more complex branching relationship of various sub-families. Furthermore, they found that mutations in certain gene families, such as the cell cycle regulators CDKN2A and CDKN2B, were associated with more aggressive tumours when transplanted in animal models and poorer prognosis when found in patients.

Importantly, the fact that the cells come from distinct families may explain some of the difficulties in treating cancer. Treatments that eliminate one genetic family may leave behind other distinct subtypes that can continue to grow and repopulate the tumour. In the cancer stem cell model, underlying stem cells are thought to drive tumour growth and eliminating these cells is a goal of therapy. Given these new results that indicate a number of genetically distinct sub-populations that make up a tumour, broader approaches that target multiple of these families could be necessary for complete cancer eradication.

January 20, 2011

A tribute to Ernest "Bun" McCulloch (1926-2011)


Mccullochb&w On January 20, 2011 Ernest (“Bun”) McCulloch passed away. Although Bun was known to the young generation of stem cell researchers only by reputation, for those of us who knew him “back then” he was an icon. “Back then” was the 60s and 70s when the group led by Bun McCulloch and Jim Till conducted experiments that led to the concept of stem cells as the source of all cell types in the blood-forming system, proved their existence, described their properties and set the stage for the life-saving procedure of bone marrow transplantation.

Back then we didn’t think much about stem cells in other tissues, and it was more than 15 years before stem cells were identified and characterised in other tissues and in the developing embryo.

Back then I was a PhD student under the supervision of Jim Till. I had come from a physics background as had Jim. Dr. McCulloch, as I called him back then, was a haematologist, a visionary, a descriptive scientist who loved to dream about the art of the possible. His knowledge of the blood-forming system was prodigious, but he was not content with its description. He wanted to know how it developed and how it sustained itself. Jim Till, being a quantitative scientist was the driving force behind the idea that to understand the biology required quantitative measurements.

So when nodules of growing cells were seen in the spleens of irradiated mice who had received bone marrow transplants, it was the two of them together who realized that these could be clones of cells derived from multi-potential precursors. We didn’t use the term “stem cells” back then. Together they set out to develop the spleen colony assay as a quantitative assay for stem cell number, to demonstrate the presence of multiple cell types in the colonies through detailed cytology and to prove that the colonies were derived from single cells. It was a very productive time, with many graduate students and post-doctoral fellows contributing to the effort. You will recognize some of the names – Andy Becker, Allen and Gillian Wu, Ron Worton, Paul Austin, Don Sutherland, Norman Iscove, Allan Bernstein, Bob Phillips, Rick Miller, and somewhat later Connie and Allen Eaves.  Many of them went on to train the next generation of stem cell biologists. 

At the beginning I was afraid of Dr. McCulloch, so I stuck to getting advice from Dr. Till. The odd time I did speak to him, I felt that he was thinking so far ahead of me that I struggled to understand. Slowly, after a great many weekly group seminars (held in the office of Lou Siminovitch until we outgrew it) I began to be comfortable speaking briefly to Dr. McCulloch, but still didn’t venture into the inner sanctum of his office. Finally, one day after I had generated my first substantial results I presented them to Jim who suggested that I tell Bun as well. I made an appointment and went to see him. He listened, agreed on the importance of the work and without hesitation began to suggest future experiments – dozens of them – so many I couldn’t keep track. This was my first real encounter with the brilliant mind and quick intellect of Bun McCulloch.

Soon I was making regular visits to his office.The next memorable encounter was when I wrote my first paper on stem cells. Like all graduate students, my first paper was way too long and had unnecessary detail that only I deemed to be important. Jim had told me that, and suggested ways to improve it. Bun had received a copy of the manuscript and invited me to his office. He agreed with Jim about the unnecessary detail, and asked if I would like to know how he would write it. I said yes. So, he picked up his Dictaphone and in the next 20 minutes he paced the floor in his office while he dictated a manuscript from start to finish. In those 20 minutes he transformed my pedantic, thoughtful, careful, and fully detailed manuscript into a lively, punchy and dramatic account demonstrating that stem cells defined by the spleen colony assay are distinct entities from the other known precursor cells of the blood-forming system. I was transfixed. It had never occurred to me that anyone could do that. To be sure, his dictated version needed some editing and polishing, but the essence of what he dictated remained intact. It was a valuable lesson, and it completely changed my concept of how to write a scientific paper, even though I never did learn to dictate them in 20 minutes.  

Even though Bun had been retired for many years, he will be missed by all of us who knew him well and admired his intellect, his dedication and his profound influence on the field of stem cell biology. For Jim Till, I am sure it will be like losing a twin who for many years had been joined at the hip. And for the younger generation of stem cell scientists it will be a time to pause and reflect on those early experiments, carried out long before the term “stem cell” was a household word, and long before the profound importance of stem cells was recognized. Bun and Jim were true pioneers whose work dictated how we think about the human body, its development and its replenishment. Bun can rest knowing that he truly made a difference.  

-- Ron Worton, former Scientific Director of the Stem Cell Network


I invite additional memories, thoughts and comments to this blog as a public, scientific memorial of the incredible Bun McCulloch.


January 19, 2011

Keeping the lights on

by David Kent

Light bulb Banned from receiving federal funds in 2004 by the Bush administration, human embryonic stem cell research was recently embraced by the Obama administration in March 2009 -- sort of, anyway. As many readers are no doubt aware, U.S. courts are currently embroiled in a debate about whether or not the federal government should be funding human embryonic stem cell research.  

If the Obama executive order makes it through the courts and federal monies (i.e.: National Institutes of Health) become widely available for embryonic stem cell research, then non-federal funding organizations (private or state) will certainly re-assess their role in stem cell research. A looming question is what will happen with the personnel and institutes that are funded by these special monies that were created when federal funding was not present –- or, in other words –- who will keep the lights on? Funders will no longer be asked to provide trailblazing monies for research that could not have otherwise been undertaken, but rather to determine if they can sustain this level of investment in stem cell research and infrastructure on top of the new federal research dollars. For many jurisdictions this decision is further complicated by the competing demands for resources as they seek to emerge from the global financial crisis. 

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January 13, 2011

Implications of court decision and research ethics policy update in Canada

by Ubaka Ogbogu

A couple of significant updates to report on from the ethics and law arena:

  1. On December 22, 2010, the Supreme Court of Canada (SCC) released its long-awaited judgment in the Reference re: Assisted Human Reproduction Act case involving a constitutional challenge brought by the province of Quebec against several sections of the Assisted Human Reproduction Act (AHRA), Canada’s premier assisted reproduction and embryo research legislation. The case came before the SCC by way of an appeal launched by the federal government against an earlier Quebec Court of Appeal (QCCA) judgment in favour of Quebec, which I have written about. The SCC judgment, which allowed the appeal in part and affirmed the QCCA decision in part, has been widely reported on—read some here

    How would the decision impact on stem cell research activities in Canada? Firstly and most importantly, the judgment decides a reference question, which means that it is merely an advisory opinion and the federal government is not legally bound to follow or implement it. However, no reference opinion has ever been ignored in Canada’s history, and it is unlikely that the feds would risk the political consequences of such an act in this instance. Secondly, Quebec’s challenge did not include the sections of the Act dealing with prohibited stem cell research technologies such as embryo creation specifically for research purposes and somatic cell nuclear transfer. In effect, those provisions remain validly enacted criminal law, and as far as the scope of legally-sanctioned stem cell research goes, the status quo remains the same. Lastly, the decision does affect the regulatory scheme for stem cell research. The SCC ruled that the federal government did not have the constitutional authority to enact provisions requiring that researchers obtain a license before engaging in controlled (regulated) activities such as transgenics and the use of in vitro embryos created for lawful purposes. This portion of the judgment leaves Assisted Human Reproduction Canada—the federal agency responsible for monitoring and licensing assisted reproduction and related research—with very little to do, and there has been much speculation that the federal government will scrap the agency. 

  2. Canada’s three research funding agencies have released an updated second edition of the Tri-Council Policy Statement, which governs the ethical conduct of research funded by public funds or conducted in institutions receiving such funds. I haven’t had time to study the document, but a cursory look revealed a number of interesting new provisions on reporting incidental findings revealed through genetic research, ethical review of multi-jurisdictional research, clinical trial registration, and a section that adopts the Updated Guidelines for Human Pluripotent Stem Cell Research for research involving pluripotent stem cells. 


January 12, 2011

Stem cells in a bottle

In an article in the Globe and Mail this past weekend, reporter Carolyn Abraham provided an interesting and under-reported glimpse into the cosmetics industry use of stem cells to market their products. She notes:

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January 04, 2011

Obama Administration issues memorandum on principles of scientific integrity

by Ubaka Ogbogu

In March 2009, in his remarks at the signing of an Executive Order to reverse the Bush-era stem cell research funding restrictions, President Obama directed John P. Holdren, Director of the Office of Science and Technology Policy, to “develop a strategy for restoring scientific integrity to government decision making” by ensuring that science policy is shaped through the involvement of scientific advisors appointed based on their qualifications and on the soundest scientific evidence, transparency and public engagement. A year and nine months later, on December 17, Mr. Holdren issued a memo to provide guidance on implementation of the principles of scientific integrity stressed by the President in his remarks. The four-page document is definitely worth a read, but I have distilled the main points below.

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