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13 posts from June 2010

June 30, 2010

Cartilage tissue engineering

by Allison Van Winkle

In the body, cartilage has minimal potential to heal itself once damaged, as the tissue is not naturally exposed to a blood supply, and is then prevented from benefiting from the body’s immune response and wound healing capabilities. By using a tissue engineering approach, researchers hope to develop replacement cartilage that can be transplanted into a patient to stimulate the regeneration of the native tissue. 

In particular, patients suffering from osteoarthritis, where the joint cartilage has worn down over time, may particularly benefit from cartilage regeneration, as opposed to current treatment methods which range from pain medication to artificial joint replacements.

A tissue engineering approach will generally combine a cell source, biological growth or differentiation factors, and a biocompatible scaffold to grow the cells on. One proposed scaffold for cartilage tissue engineering involves using natural materials derived from healthy cartilage tissue, known as extracellular matrix. 

A recent study published in Biomaterials reports that the extracellular matrix scaffold strongly supports cartilage cell development. The researchers used rabbit mesenchymal stem cells in combination with an extracellular matrix scaffold, developed from healthy porcine cartilage, and found that cartilage-cell development from the mesechymal stem cells occurred earlier in the extracellular matrix scaffold, and produced more cartilage-like tissue compared to a synthetic scaffold.

One complication of this method is that it is difficult to reproduce the exact conditions; as the matrix was derived from a variable animal cell source, the exact composition of the scaffold, as well as mechanical properties and porosity are likely to vary in some degree in each experimental run. The effects of this variation, however, may not impact cartilage cell formation, as the animal-derived matrix outperformed the more defined synthetic scaffold. 

Future related research will hopefully further examine this potential variability, and apply these findings to human tissue.

June 28, 2010

Induced publication of stem cells?

by David Kent

Earlier this month, the New Scientist shook up the stem cell community, putting forth the idea that publication speed, frequency, and journal quality might be skewed by where you’re from and who you know rather than the quality of your data.

The article, entitled "Paper trail: Inside the stem cell wars" was inspired by an open letter last summer (notably co-signed by Austin Smith, Shinya Yamanaka, Thomas Graf, Connie Eaves and Guy Sauvageau, among others) which requested leading journals to publish the reviews of papers in order to increase transparency and to reduce “unreasonable or obstructive reviews” – something that is already done by the EMBO journal. This is an issue that I have blogged about before.    

There was a large amount of attention to this story over the past year, including a BBC news radio story worth listening to.  This includes Prof. Peter Lawrence decrying the current system as a “corruption of modern science”. 

The New Scientist article took an interesting approach to investigating the consequences of such a system and analyzed over 200 papers in the new and high flying field of induced pluripotent stem (iPS) cells, focusing on the dynamics of publication (time from submission to acceptance, networks of citations, etc).  The data analysis in the article can be stripped down to two main points regarding publications involving iPS cells:

  1. A US scientist, on average, will be published faster in more important journals when compared to a non-US scientist. This is statistically significant – there appears to be a lag of almost one month for a non-US based scientist.
  2. International scientists do not have citation networks amongst themselves to the same degree as US based scientists.  

The article speculates that US-based researchers have supported each other through a vast citation network that makes it attractive for journals to accept papers from these scientists.  It doesn’t take much to conclude that if journals want to give their impact factor a boost they would look favorably on publishing papers from scientists at one of these citation nodes.

Naturally, a story like this gets you thinking, so I did some quick investigative journalism.  I’m often struck by how novel research is completed by multiple non-related groups at the same time and wondered if this trend that the New Scientist reported was at the crux of these situations in my own field of adult stem cells.  The first two examples of two groups pursuing a similar story that I put to the test made me groan in agreement:

  1. Group A from Asia submits to a high level journal on June 17, 2009, accepted April 8, 2010, published April 26, 2010.  Group B from the USA gets “contributed” to PNAS on January 21, 2010 and is published online March 18, 2010 (the “contributor” just happens to be the former supervisor of the last author). 
  2. Group A from Europe submits to a high level journal on July 25, 2008, accepted October 30, 2008, published December 4, 2008.  Group B from the USA submits on November 24, 2008, accepted December 1, 2008, published December 5, 2008 – yes that’s right:  less than one week from submission to acceptance and another week to publication.

While I would normally say to myself, “surely these are exceptions and not the rule” and note that these are four different journals with unique review processes, The New Scientist article strongly suggests that this sort of journal jockeying is actually quite pervasive and for that reason, this article should be read by everyone who is involved in the peer review process in hopes that we can determine why such a trend is in existence and if something foul is afoot, set it right.

June 24, 2010

NAS guidelines revised; more turmoil at AHRC

by Ubaka Ogbogu

NAS revises stem cell guidelines: The US National Academy of Sciences recently released amendments to its influential and widely adopted voluntary Guidelines for Human Embryonic Stem Cell Research. This is the third set of amendments since the guidelines were first issued in 2005 (previous amendments were issued in 2007 and 2008). Key revisions include:

  • The guidelines now apply to derivation or research use of hESC lines from morulae, parthenogenesis, or androgenesis. Prior to the amendments, the guidelines applied only to hESC lines derived from blastocysts and SCNT into oocytes.
  • Research involving the introduction of hESCs into nonhuman primates at the fetal or postnatal stage of development is now permissible following ESCRO review and approval (in addition to conventional reviews by institutional IRBs, Animal Care and Use Committees, and Biosafety Committees.
  • Written evidence that a gamete donor agreed at the time of donation to allow future use of blastocysts and/or morulae resulting from their donation for embryo research is now sufficient proof of consent. 
Other provisions of the Guidelines remain unchanged, including the ban on compensation for oocyte or embryo donation, ESCRO review, and obtaining consent from all gamete donors prior to research. 


Further resignations at AHRC: Following my earlier post on the implications of the resignation of two members of the Board of Assisted Human Reproduction Canada for stem cell research oversight in Canada, Irene Ryll, the consumer representative on the Board, also resigned. The Board is now left with seven members with no direct and relevant expertise in key areas within the agency’s mandate, and who do not represent the interests of those most directly affected by their activities. Clearly, this raises very serious questions about the legitimacy of the Board. Although the Assisted Human Reproduction Act – the legislation that governs the existence of the Board – only specifies maximum membership (13), it does require that Board membership “reflect a range of backgrounds and disciplines relevant to the Agency’s objectives.” In my opinion, the constitution of current board does not meet this requirement. Also, given that the Act forbids those who hold or apply for licenses to conduct activities regulated by the Act, or their affiliates, from serving as Board members, it is doubtful that replacement appointees will be chosen on the basis of relevant background and expertise.

June 19, 2010

The hot seat in San Francisco - the last word

And the last word (or words) goes to Fabio Rossi of the University of British Columbia. So ends a great conference!


The hot seat in San Francisco - part 4

Our couch is just too inviting... more comments on ISSCR 2010 from Mike Kallos of the University of Calgary and Feodor Price of the Ottawa Hospital Research Institute.



The hot seat in San Francisco - part 3

More ISSCR meeting insights from James Ellis of Toronto's Hospital for Sick Children and Michael Rudnicki, Scientific Director of the Stem Cell Network.

June 18, 2010

The hot seat in San Francisco - part 2

More thoughts on the ISSCR conference in San Francisco from the attendees. 

The hot seat in San Francisco- part 1

We're a the ISSCR meeting in San Francisco inviting folks to stop by the Stem Cell Network booth (number 509), sit on our comfy couch and talk about what they've enjoyed the most at the 2010 ISSCR annual meeting. Featured here are Bernard Thébaud of the University of Alberta and Rebecca Skinner of the Australian Stem Cell Center. Stay tuned, more to come...

June 17, 2010

Adult stem cells keep you roadworthy

By Francina Jackson

car on road How do adult stem cells work? In healthy tissue the adult stem cell population lies dormant. Dormant stem cells are activated by external trauma signals, which trigger patterns of gene expression and protein biosynthesis, thus activating the stem cells to multiply and regenerate damaged tissue. If you think of your normal tissue as a car, then the adult stem cells are the spare parts you keep in the trunk. Usually your car works well on its own, but occasionally one part or another might wear out and need replacing. Malfunctioning tissues are in a constant state of disrepair and must therefore undergo repeated cycles of regeneration. These cycles place a strain on the stem cell population, often leading to its precocious depletion and a permanent state of tissue degeneration. So, in this case, you have a car that breaks all the time and has a finite number of spare parts in its trunk (which you quickly exhaust). With minimal contention, you accept that your car is a lemon but, as it is the only one you've got, you must begin pursuing more creative avenues to keep it on the road.

Researchers too must be creative as they choose among different approaches for developing therapeutic strategies. One tactic is to identify the genetic basis for the cellular malfunction and correct it within the patient's own stem cell population using gene therapy. This is done to bolster mature tissue function by ensuring that the regenerated portion of the tissue is not fraught with the same deficiencies as the original tissue. Essentially, you are taking a spare part from the trunk and fixing it before using it to fix your car. 

Another approach is to transplant a healthy population of donor stem cells into the dysfunctional tissue. In this case the hope is to fix the defect whilst bypassing the shortcomings inherent to the original tissue. In other words, you decide to get your spare parts from another, and hopefully better, manufacturer.

While both gene therapy and transplantation have merit, neither is perfect. Here my analogy falls short because attempting to identify a malfunction in a cell can in no way be compared to troubleshooting a malfunctioning automobile. Three simple reasons for this are:

  1. We have only the tip of the iceberg in terms of understanding how cells work (unlike cars, for which we have expertise and blueprints); 
  2. Cells are orders of magnitude more complex than any automobile, with millions of dynamic interactions and cellular processes occurring each moment to sift through; and 
  3. Unlike a car, the successful identification of a cellular problem is not always synonymous with the identification of its practical solution (in fact, it often represents years of further research and unanticipated conundrums). 
While stem cell transplantation should bypass these problems, its two main concerns are that transplanted cells might be rejected (the spare parts from the alternate manufacturer are simply incompatible), or that they might differentiate in an incorrect and uncontrolled manner resulting in a tumour.

Researchers do have their work cut out for them in developing stem cell blueprints (the automobile itself has been a work-in-progress for over a century), however networks such as this are certain proof that they are up for the challenge.

June 14, 2010

A revised map for blood development

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Please check it out on its new home, Signals BlogA revised map for blood development