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11 posts from November 2010

November 29, 2010

What do you think of stem cells?

by Michelle Ly

I was having my bathroom renovated a few months ago and got into a discussion with my contractor about work. I mentioned that I had done some work with the BC Cancer Research Centre and other biomedical research institutes. His comment was, “Cancer research? So do you do any stem cell work? That's scary stuff eh?”


I admit, I had never thought of stem cells as being scary. To me, stem cells are still a nebulous sort of work-in-progress – the road to possibilities, sometimes lined with controversy over ethics or funding, but scary? Never. But to my contractor, it was that same seemingly limitless potential that was scary. It led me to wonder, what did other people think of stem cells? This was the informal, open-ended question that I put out to readers of my personal blog and social networking sites.

Most people, regardless of their background or occupation, were enthusiastic about the potential for stem cells to propel science and research in new directions. A nutritionist wrote: “Stem cells are a vital component to modern health sciences research. The ability to transform these cells to fit our needs are instrumental in the development of new treatments for diseases such as Parkinson's where there is no hope of a conventional cure.” This sentiment was echoed by many other posters who cited potential cures and new therapies as reasons for pursuing stem cell research.

A commenter from the US who is interested in law and ethics remarked: “... economically – it did a LOT of things for my university (UW-Madison) and surrounding communities where the first line of human embryonic stem cells were discovered. […] We have a huge amount of development in our biosciences departments because of it, which creates a lot of job and investments in the local area.”

The need for continued research was also emphasized. Kate, a graduate student with a background in chemistry writes: “Like so many things in science, stem cells are not completely understood. In fact, this is an understatement. What we actually know about stem cells - how they develop, what they do, where they come from - only scrapes the surface.” One post-doc felt that there was perhaps too much hype around stem cells. In her view, they represent  potential for the development of future therapeutic and research techniques, but they are not the cure-all some people might think. Indeed, recent commentary in the New York Times on the value of basic science) echoed these sentiments.

As a relatively new avenue of research, several people mentioned the need for clear, scientifically sound regulations, both to ensure the progress of science and the avoidance of a moral slippery slope. A few readers questioned the many “stem cell clinics” offering untested treatments for diseases and aesthetics, with one wondering, “How can I choose what's best for myself when the experts seems to be constantly disagreeing?” The web site, www.closerlookatstemcells.org, published by the International Society for Stem Cell Research is an excellent resource for those with questions about stem cell treatments. 

The take-home message seemed to be hope, tinged with caution. Like a lot of basic science, there is potential for greatness once underlying mechanisms are understood, research techniques improved, and new strategies devised. I invite readers here to submit their thoughts – What do you think of stem cells?


More from the Scientific Meeting

If you didn't have the chance to attend the Stem Cell Network's scientific meeting in Calgary last week, you can get first hand accounts of the best the conference had to offer. If you were there, then there's nothing wrong with experiencing it again, is there? Have a look at what Fabio Rossi of the University of British Columbia, and Ubaka Ogbogu of the University of Toronto had to say:



November 24, 2010

At the SCN 2010 Scientific Meeting: Xin (Kevin) Wang

There's been all sorts of fun so far at the Stem Cell Network's 2010 Scientific Meeting, and we've been talking to a few of the attendees about what their thoughts are on what's happened so far. Late on day two, we spoke with Kevin Wang of Sheila Singh's lab at McMaster University about his experience:

November 23, 2010

SCN scientific meeting: Day 1

It may be cold in Calgary but there's plenty of warmth and amicable conversation at the Stem Cell Network annual meeting. Day 1 opened with an afternoon plenary featuring some impressive talks. Peter Lansdorp of the BC Cancer Agency gave an overview of his current work in epigenetics and Mickie Bhatia of McMaster University presented on his recent findings on the direct conversion of skin fibroblasts to blood cells, as was recently published in Nature. The opening talk from Jonathan Moreno of the University of Pennsylvania highlighted the current state of public policy with regard to pluripotent stem cell research, particularly in the US. This was later followed by the Till and McCulloch Lecture by the University of Alberta's Timothy Caulfield, who spoke specifically about the what he envisions will be future challenges in policy arising from iPS research.

Other events on opening day included the Own the Stage workshop for developing presentation skills, which also featured ten lightning round research presentations from selected SCN trainee abstracts, the Career Mixer networking event, poster presentations and the opening of both the exhibit hall and the Cells I See art gallery. 

Caulfield Till & McCulloch lecturesm
Timothy Caulfield presenting the Till and McCulloch Award lecture

TCC booth
The Trainee Communications Committee table in the exhibit hall

Cells I See Gallery sm
The Cells I See Art Gallery. Attendees each get a ballot and select the winner via blind judging.

November 20, 2010

Watching the watchers

by Chris Kamel

Because of some vocal opposition, stem cell research is no stranger to controversy. Usually this comes in the form of protests or government lobbying, but Nature News is reporting the story of a group that is trying to discredit the scientists themselves.

The anonymous group, calling themselves Stem Cell Watch, has sent out emails calling into question published stem cell research and accusing authors of photo manipulation and fraud. Despite the anonymous accusations made outside the usual channels, the journals in question are looking into the matter and have found no evidence of wrongdoing and authors have been cleared. Allegations of fraud are no laughing matter and can be extremely damaging to a scientific career.

The scientific enterprise relies a great deal on trust - trust that researchers are reporting results truthfully, and trust that review and criticism is done in an honest way. Scrutiny and skepticism are essential to the process, but need to be done in good faith. Whether the Stem Cell Watch accusations are from a group with a particular stem cell agenda, or simply the result of overzealous students is unclear, what is clear is that they were neither accurate nor helpful. As UK stem cell researcher Robin Lovell-Badge puts it, "Although we don't want fraudulent work to be published, this group does not seem to have the skill or knowledge to make a fair assessment."

This kind of uninformed criticism and indiscriminant accusation works against the interests of open and trustworthy science. It also highlights the need for good stem cell research (and science in general) resources to counter this type of misinformation. We shouldn't need watchdog groups for the watchdog groups.

Stem Cell Watch is not associated with the The International Cellular Medicine Society website of the same name.


November 17, 2010

Can stem cells end the need for blood donors?

by Paul Krzyzanowski

In a previous post, Chris Kamel recently reviewed the Nature article about direct creation of blood progenitors from skin fibroblasts as discovered by Mick Bhatia's research group. The fascinating thing about this article is the potential for enabling autologous cell treatments with a reduced risk of iPS-cell-induced cancer.

Certainly, no one can deny that creating a clinically usable substitute for matched bone marrow from a person's own skin cells would be a phenomenal accomplishment. In my view, what this advance can really accelerate is work to produce methods of culturing human hematopoietic stem cells with the goal of producing artificial whole blood. Bioreactors are routinely used to expand hematopoietic stem cells and producing whole blood is only a (large) step away.

The demand for blood and blood substitutes is large and growing. According to the American Red Cross, approximately 15 million litres of blood were used in transfusions in 2006, and that's only taking the United States into account. This amount is expected to grow in the future, and with the individual components of whole blood having short shelf lives -- six weeks for red blood cells and only one week for platelets -- a constant supply of blood from donors is needed.  

Dr. Dana Devine, Vice-President of Medical, Scientific and Research Affairs at Canadian Blood Services said that cultured blood products might someday help part of this need. "There is a lot of transfusion research science currently ongoing worldwide " she said, noting that the use of skin derived stem cells to replace autologous blood cell collection might be possible for patients with adequate time to wait for cell culture (for example those undergoing elective surgery or chemotherapy), however “the tissue engineering and scale-up issues in turning these kinds of research scale studies into a cost-effective product remain a challenge.”  

The volume of blood required for some procedures is surprising: a liver transplant procedure might use up to one hundred units (45 litres) of blood, according to the Canadian Blood Services website. As less than 40% of the population is eligible to donate blood, those in need of rarer blood types may be out of luck if an appropriate donor hasn't recently come forward within the same geographical location.  

As well known medical procedures, blood transfusions serve two major purposes. One is to replenish volume from blood loss after trauma or during surgery, while the other is to restore the oxygen carrying capacity of the circulatory system. Most volume-expanding blood substitutes are more or less salt solutions, which don't restore the oxygen carrying capacity provided by red blood cells. The products that actually do restore this capacity are divided between perfluorocarbons and various hemoglobin solutions, the latter usually derived from bovine blood.

However, development of bovine hemoglobin products hasn't been easy. None are approved for general use, and those undergoing clinical trials today are in no way guaranteed to gain approval. Up until recently, Biopure was a company producing Oxyglobin, a viable oxygen-carrying product approved for veterinary use, but primarily pursuing approval for a similar product for use in humans called Hemopure. Failing to get approval, the company began to run out of funds in early 2009 and filed for bankruptcy soon thereafter. Some may also recall the Canadian company Hemosol (Now Hemosol BioPharma) formed in the 1980's to commericialize Hemolink, a human hemoglobin based oxygen carrier. Like Biopure, Hemosol filed for bankruptcy in 2005, and both were examples of firms developing their products over the span of two decades or more. Many other blood substitutes like these have been pulled from trials due to safety concerns, including vasoconstriction and pain accompanying their transfusion. 

Producing blood from stem cells may finally be the technology that becomes successful in this space, as erythrocytes (red blood cells) can be produced from human iPS cells. These laboratory studies are establishing principles to show that red blood cells can be generated on a larger scale, and raise the possibility that, in the future, problems of limited blood supplies being available may be reduced or nearly eliminated.  "Though we currently don't have ongoing shortages of blood products in first world blood systems" said Dr. Devine, "there are significant shortages in the developing world."

"However, for the foreseeable future, we still need blood donors to make the system work."


November 10, 2010

The Royal Society and the philosophy of openness: Are we moving backwards?

by David Kent

One of the most memorable moments of my PhD training was at a 2006 Keystone conference where Shinya Yamanaka presented a little something called Pluripotency and Nuclear Reprogramming. He carefully presented the transcription factor screen that would culminate in the first re-programming of a skin cell into a pluripotent stem cell (iPS cells). It was in the mouse, but as the publication trail shows, human iPS cells were not far behind. Having full knowledge of how important this discovery was and how simple the technique was to replicate, Yamanaka had elected to present the transcription factors used in the screen as letters "A" through "X" instead of the actual gene names. While the room certainly stirred as people realized the therapeutic possibilities of such a technology, a more impressionable moment for me was a rather saucy comment that popped up in the question period: 

“This is great Shinya. You know… our lab has also worked with factor M and have obtained very similar results – what are the other factors?”

After a good-natured chuckle, the audience quickly realized that the factors were not to be named that day and we all went back into the dark waiting for the research paper to be published. 

Let it be put on the table that I have an enormous amount of respect for Shinya Yamanaka and his team of scientists – they uncovered something amazing with iPS cells that will certainly drive much future scientific research. But this single event of holding back data stopped the emergence of the iPS field dead in its tracks for months. I realize why it was done, and I recognize that there was a pretty reasonable chance that the discovery would be poached by someone else – so fair enough, right? I filed these feelings away, until…

Late last month I attended a Royal Society Meeting entitled What’s Next for Stem Cell Biology where Kazutoshi Takahashi (the lead author on the original Yamanaka study) gave an excellent talk on the newest developments in his research which highlight a gene that potentially distinguishes “good” iPS cells from “bad” iPS cells (i.e.: prospectively identifying those lines that are likely to cause tumor development). Which gene was up there on the big screen?  Gene X. 

Of all the places to present a “gene X” – the Royal Society venue seems particularly egregious. A society with a 350 year history of openly discussing topics of scientific interest with one of its five priorities being to “increase access to the best science internationally” seems a likely advocate against such blatant acts of non-disclosure? However, it seems the organizers and scientist participants were perfectly okay with this brand of discussion – not even a cheeky question this time.

Again, I understand the reasoning behind keeping your cards close to your chest – but surely something is wrong with the system if we have to wait for months and months of reviews and publication before getting such information into the hands of other scientists. Have we entered (and embraced) an era of scientific research where one’s career path is tantamount to moving science forward? If so, I think we desperately need to question our motives for being in medical research in the first place.

Colleagues with whom I have shared these views shrug their shoulders and tell me it’s better to have a funded lab and hold back research than to have no lab at all (which apparently is the fate of those unfortunately “scooped”). I’m not convinced though. To me, when you are confident in the results that you observe, it behooves you to share them with the research community despite any amount of you-might-not-get-a-lab rhetoric. Hopefully we’ve not traveled too far down this path to avoid turning back.

November 07, 2010

Skip the iPS middle man: Direct conversion of skin fibroblasts to blood progenitors

By Chris Kamel

Heather Heine image, UBC Though methods to convert adult cells into induced pluripotent stem (iPS) cells continue to improve, transition from the lab bench to the clinic can be a trickier proposition. Due to imperfect efficiency, each manipulation -- conversion of adult cell to iPS cell to cell lineage of choice -- decreases the yield of the cells of interest. This is further complicated by the fact that iPS cells can retain an epigenetic memory of their progenitors which can limit their differentiation potential.

Work out of Stem Cell Network researcher Mick Bhatia's lab in the Stem Cell and Cancer Research Institute at McMaster University, published today in Nature, suggests that it is possible to skip the middle man, iPS cells, and convert differentiated adult cells directly into different cell types.

The authors demonstrated that expression of the stem cell transcription factor OCT4 in fibroblasts, one of the factors required for reprogramming to iPS cells, resulted in a number of colonies resembling hematopoietic cells and expressing the hematopoietic cell marker CD45. Until now, OCT4 had previously not been implicated in blood development. Further, the effect was not seen with expression of other iPS reprogramming factors. By looking at expression of genes involved in induction and maintenance of pluripotency throughout the transduction process, the authors were also able to demonstrate that the resulting hematopoietic-like cells arose without entering a pluripotent state, avoiding conversion to stem cells then back to blood lineages. Finally, the resulting cells were shown to be able to form colonies and differentiate into myeloid cells in vitro, and were able to engraft in a mouse in vivo, indicating the cells behave and mature like normal hematopoietic progenitor cells.

The ability to skip conversion to iPS cells, a potentially inefficient and yield-decreasing step, may also improve the safety -- and therefore clinical feasibility -- of autologous cell treatment. Because these cells never enter a pluripotent state, they were shown to not give rise to teratomas, and the resulting engraftments lacked leukemia stem cell properties, this suggests a decreased cancer risk compared to other alternatives that retain tumour potential. The ability to directly convert adult cells to blood progenitors, while avoiding some efficiency and safety concerns, could provide an important and interesting basis for future cell replacement therapies.

Image by Heather Heine, UBC. Cells I See collection.

November 05, 2010

Making livers in the lab

By Katie Moisse

In 2009, surgeons transplanted 2,155 organs -- nearly a quarter of which were livers - from live or deceased donors into grateful recipients. Sadly, another 3,796 Canadians remained on the transplant wait list, and 249 died while waiting, according to the Canadian Organ Replacement Register.

To help mitigate the organ donor shortage, scientists are looking for ways to create bioartificial organs by seeding human cells onto transplantable tissue scaffolds. For the first time, researchers have generated functional mini-livers by growing primary human fetal liver progenitor cells and endothelial cells on a decellularized liver scaffold -- the skeleton of a liver, complete with connective tissue and blood vessels -- from a ferret.

The researchers, from Wake Forest University in Winston-Salem, North Carolina, fed the human cells (70 million human liver progenitor cells and 30 million endothelial cells) into the ferret liver bioscaffold through the portal vein and placed the hybrid organoid in a bioreactor constantly perfused with fresh culture medium for a week. The cells seeded in multiple, thick clusters throughout the bioscaffold and began to function like liver tissue, expressing albumin and a host of other liver cell markers. Lead author Pedro Baptista presented the team’s preliminary findings October 30 at The Liver Meeting (formerly the American Association for the Study of Liver Diseases annual meeting) in Boston.

Another research team, from Massachusetts General Hospital, Harvard Medical School and Shriners Hospitals for Children in Boston, used a similar approach to reconstitute a decellularized rat liver with adult rat hepatocytes and endothelial cells, with the ultimate goal of transplanting a functional bioengineered organ into a rat. However, neither group was able to repopulate more than a third of the bioscaffold with cells.

Using decellularized tissue to engineer organs in vitro has tremendous potential though, because it allows scientists to take advantage of the organ's existing, often complex vasculature. Furthermore, in the absence of cells, organs' skeletons are relatively non-immunogenic. This means, for instance, that decellularized pig livers seeded with human cells could potentially bypass the organ rejection problems linked to xenotransplantation (interspecies transplantation). In the meantime, getting more cells to seed onto these organ scaffolds, fostering their ability to function like proper organs and nursing their ability to withstand the transplant process and survive long-term are goals more realistic than ever.


November 03, 2010

Stem cells back on Parliament's agenda

Yesterday, for the first time in seven years, the House of Commons Standing Committee on Health heard testimony on the current status of stem cell research in Canada. Although the topics covered by MPs during the Committee hearings did not seem to reflect any immediate legislative priorities, nevertheless it was a welcome opportunity for the stem cell community to provide input to Parliament. Three members of the Stem Cell Network gave testimony during the proceedings:

Dr. Michael Rudnicki, Scientific Director of the Stem Cell Network, talked to the recent advances in science, noting in particular the profound impact of the discovery of iPS cells, the increasing use of stem cells to screen for new or safer drugs, and the clinical trials anticipated over the next five years. A full copy of his remarks can be downloaded in both French and English.

Drew Lyall, Executive Director of the Stem Cell Network, and Board Chair of the Canadian Stem Cell Foundation, spoke next about the opportunity stem cell research represents for Canada to improve patient lives, reduce the economic burden of health care, and create new jobs. However, he also warned that Canada risks losing its leadership in this field without further substantial investment from the federal government. A full copy of his remarks are available in French and English.

Finally Dr. Janet Rossant, Chief of Research at SickKids Hospital in Toronto, and Deputy Director of the Stem Cell Network spoke about some of the regulatory challenges to the research environment, in particular the overlapping mandates of the Assisted Human Reproduction Agency of Canada, CIHR’s Stem Cell Oversight Committee, and the Tri-Council Policy Statement on research ethics. Dr. Rossant also spoke to the ongoing uncertainty caused by the absence of a decision from the Supreme Court of Canada on the constitutionality of the Act with respect to assisted human reproduction. A full copy of her remarks can be found here.

Testimony was also given by Cancer Care Manitoba, in particular by Dr. Dhali Dhaliwal, President & CEO, and Dr. Donna Wall, a physician in pediatric hematology/oncology.

Beyond issues relating to research advances, the funding environment, and regulation, a number of other topics were touched upon in some depth:

  • Potential opportunities to increase participation, particularly amongst minority groups, in OneMatch the Canadian bone marrow transplant donor registry managed by Canadian Blood Services. It is an area in which Joy Smith, Chair of the Committee has taken a particular interest.
  • The need to establish a Canadian public cord blood bank, and the challenges in securing funding from the Provinces and Territories to do so, despite unanimity amongst them that it needs to be done.
  • The risks face by Canadian patients seeking therapies from clinics outside of the country, offering therapies for which there is little scientific evidence. This issue of “stem cell tourism” is one we have discussed before.
  • Members also enquired about the Stem Cell Charter, a call to action for scientists patients and the public prepared by the Canadian Stem Cell Foundation, asking signatories to voice their support for stem cell research. To date over 4,000 people have signed the Charter. 

While everyone recognizes the ongoing constraints imposed by the current fiscal environment, more can still be done to support stem cell research, and to advance therapies to the clinic more rapidly. Stem cells are back on Parliament’s agenda, so if you feel strongly write to your MP, or directly to one of the Members of the Standing Committee.