We've got a new niche!

The SCN Blog has a new name and a new home: http://www.signalsblog.ca

After nearly four years and 207 blog posts, we finally outgrew our dish, so to speak. Late last year, we began planning with the newly-formed Centre for Commercialization of Regenerative Medicine, who indicated an interest to begin blogging in the sphere. (Perhaps you'll recall our name contest?) Why have two blogs competing when one can do the job? The result is Signals Blog (the new name came from an SCN staff member who sadly was not eligible for a prize), which will continue to bring the same level of insight, commentary and research news you've found on the SCN Blog, but will add new perspectives and news on biomaterials, regenerative medicine and commercialization.

We think it's a great partnership that will provide a more comprehensive view of the world of stem cells and regenerative medicine. 

To ease the transition for readers, all archived posts from the SCN Blog have been moved to their new home and RSS feeds will be updated to the new address. Comments will be closed on this site, but we'll keep a copy of the archives here for the short term. 

This is our final post on this site: please update your links and check out our new niche at www.signalsblog.ca!

2012 Cells I See winners

By all accounts, the 35 entries in this year's Cells I See Art Contest & Gallery Showing were among the best we've ever had. Certainly, there were more than we'd ever seen before (view them all here) -- so many, in fact, that we had to clear an entire lounge space at the host hotel just to set up the gallery. Of course, it was worth it, as nearly 200 people took the time during an already busy Till and McCulloch Meeting to view the entries and vote. And here's our winner:

Grand Prize (as determined by blind judging at the Till and McCulloch Meetings):

"Neuronal Wave" by Renee Head (Hospital for Sick Children, Toronto)

Description: Stem cells often lift off the glass slides they are grown on. These stained cells (Nestin and Sox2) formed, what I call my “neuronal wave”.

You might also recall that we had a little Facebook competition going as well, in advance of the meeting. This online contest collected more than 1,250 likes and shares, and brought us our first People's Choice award:

People's Choice (as determined by Facebook likes as of 8pm EST on April 27, 2012):

"Crystal Violets" by Holly Wobma (University of Calgary)

Description: This artwork represents skin-derived precursor (SKP) cells, which were captured growing on Cytodex 3 microcarriers in a floral arrangement. These microcarriers wer then "pulled" to look more petal-like in Adobe Photoshop CS5, and the floral image was isolated and pasted onto a pleasant background. The cells were stained with Crystal Violet. The name of this art thus represents the shape (floral), colour (purple) and transparent (crystalline) appearance of the flowers.

Congratulations to both winners!

View from the floor 5: Pushing the boundaries with technology

by David Kent

The final day of the 2012 Till and McCulloch Meetings was packed with great science, but a common theme definitely emerged – technological advances are changing the way we think about and perform scientific research. Keynote speaker Helen Blau issued a warning about trying to mimic the stem cell niche outside the body, using an entertaining analogy of her son’s room being a niche and invoking the image of a mother trying (poorly) to reconstruct it. She catalogued her group’s recent efforts to understand the microenvironment of a stem cell and the discovery that stem cells performed rather poorly on rigid surfaces (such as the plasticware we typically use in labs) building on the their muscle stem cell paper in Science a couple of years back. Blau stressed the importance of using new technologies like hydrogels, bound substrates, and 3D surfaces to better design the “room” of a stem cell.

In the afternoon, conference delegates were treated to talks from Carl Hansen and Timm Schroeder who spoke about microfluidics and live cell tracking respectively. Hansen, a self-labeled biological “plumber”, preached the good news of small-scale biology.  Through a series of rapid developments over the last decade, the technology pioneered out of Steven Quake’s lab at Stanford has emerged as one of the best ways for biologists to test simultaneously the properties and functions of their cells. Hansen asserts that doing small-scale reactions (nL to pL volumes) reduces the chance of introducing biological variation and saves oodles of cash, driving home the sales pitch with the detection of transcripts at the single molecule level. Hansen (and his PhD student Veronique Lecault earlier in the meeting) highlighted recent papers describing the development and use of several microfluidic devices (high throughput qPCR), and single stem cell cultures that had the crowd buzzing with questions like “when can I get this in my lab?"

Till & McCulloch Meetings 2012: Lessons to learn from leukemic stem cells

by Alexey Bersenev    

The first plenary session of the Till & McCulloch Meetings was dedicated to cancer stem cells. John Dick opened the session by asking a question: “Stem cells in cancer: do they matter?” He is always ahead of time, very precise and innovative and I think cancer stem cell researchers can learn a lot from the Dick’s studies of leukemia and hematopoiesis.

Dick’s group has showed that cancer stem cell properties ultimately govern survival of patients with acute myelogenous leukemia (AML). Stem cell expression signatures can stratify patients and direct the treatment strategies. In Dick’s study, high expression of “leukemic stem cell signatures” was tightly associated with poor prognosis and decreased patient survival. He said: “If cancer stem cells are only cell type within the tumor capable to sustain clonal growth, we should study them.” So, the first take home message -- cancer stem cells are relevant, if their properties precisely govern clinical outcome.

The cancer stem cell field is full of scientific controversies. Dick pointed out that the most controversies are coming from lack of our understanding of normal stem cells. He spent a great amount of time for studying normal hematopoietic stem cells and developing assays. His work progressed from prospective isolation and defining the markers to functional assays, from normal to leukemic stem cells. Comparing markers and gene expression signatures, his team was able to tackle similarities and differences between normal hematopoietic and leukemic stem cells. So, in order to succeed in studying of cancer stem cells, look at their normal equivalent and understand it first.

View from the floor 4: Risk aversion in cell therapy development

by Paul Krzyzanowski

On day two (May 1) of the Till and McCulloch Meetings, Dr. Emily Culme-Seymour from the London Regenerative Medicine Network introduced work that leverages previous clinical trial information to support future cell therapy efforts. In an analysis of almost 3000 clinical trials extracted from clinicaltrials.gov, Culme-Seymour focused on cell therapy related trials. She found that half of the trials were in Phase 1 (40% were Phase 2 and only 10% were Phase 3), and almost three quarters of all cell therapy trials being conducted in the United States. 

With an overwhelming majority of cell therapy trials being found at
 relatively early stages, it suggests that that
 risk-aversion is partly involved in keeping cell therapy trials from
 launching Phase 3 trials. The idea of risk aversion was rearticulated with the finding that a significantly larger proportion of trials were of transient cell therapies such as Osiris’ Prochymal as opposed to permanent cell replacement. Culme-Seymour found that only 5% of trials were testing permanent therapies.

The numbers between autologous and allogeneic trials are approximately balanced.

The most basic conclusion is that future recipients of approved cell therapies will likely need repeated treatments to maintain efficacy. Permanent cell based treatments that will act as a one time “repair” will probably remain uncommon, at least for the near future.

Temporary cell based treatments may not be a bad thing overall. 

I believe the bias towards transient therapies to be a symptom of two factors: relative ease of their development and caution on the part of the community. 

Culme-Seymour explained that it’s less complicated to develop a technology that safely produces a temporary benefit. I would extend that to say that modifying, reversing, or even upgrading transient therapies for indications will be relatively easy while changing permanent modifications presents a whole new set of problems, namely how to undo the modification before the subsequent treatment.

I definitely don’t buy the argument that a commercial desire to sell (and re-sell, and re-sell) treatments to individuals drives the development of transient therapies versus permanent ones; it’s just a matter of what technology is currently available. Dr. Culme-Seymour’s work provides an excellent roadmap for those interested in following the prevailing trends in regenerative medicine product development.  

See also:
Clinical translation summary at Stem Cell Assays
Meeting Summary 3: Anticipatory ethics and the problem of expectations
Meeting Summary 2: Commercialization plenary
Meeting Summary 1: Commercialization plenary

 

View from the floor 3: Till & McCulloch Meetings

Anticipatory ethics and the problem of expectations 

by David Kent

One of my favorite things about Canadian Stem Cell Network meetings (now renamed the Till and McCulloch Meetings) is the integration into the main programming of Ethical, Legal, and Social Issues (ELSI). It forces scientists to think outside of their own research and gives ELSI researchers exposure to the latest developments in stem cell biology. This year has been no exception and two things that rose to the top for me were a call to pursue “anticipatory ethics” and the problem with expectations.

First, a juggernaut in the field of stem cell ethics, Bartha Maria Knoppers, gave a wonderfully inspired talk on building stem cell research into a common public good. She referred to examples of common tools, biobanking, and standards for oversight and accountability to make the case for building the “infrastructure” of science. More practically, though, she stressed the importance of forward planning and this is where the concept of anticipatory ethics came up. 

Knoppers asserts that while reactionary ethics are the typical standard (i.e.: something bad happens, let’s make some rules so it doesn’t happen again), anticipatory ethics is much more dynamic and prospective. It requires a strong trust relationship, which must be actively cultivated in order to steer the science earlier (and get a better, more agreeable, set of regulations in the end). She calls for a revolution where a scientific community works together in advance to build a normative model that has gone through filters inside and outside of the field before implementation (and not driven by the need to have a rule in place with immediacy). Following the talk, Michael McDonald stressed the importance of building in feedback.  How were individuals and populations affected in post-implementation?  There is a deep need to build it into the governance, otherwise it will quickly be out of touch with social need -- it must revisit and change over time.  In my opinion, it is exactly this sort of dialogue at a science meeting that will build the trust and inspire the participation needed.

Secondly, Tania Bubela from the University of Alberta spoke about her research on the large gulf between expectations for stem cell research between the public, patients, and policy makers and the reality of the science. The expectations are being built up not just by news agencies but are also cropping up in mainstream media -- including Grey’s Anatomy, which has introduced regenerative medicine (artificial hearts and bones) and cell therapy (islet cell growth and transplantation) as though they were right around the corner. Bubela’s group has undertaken extensive analysis (text mining, longitudinal studies, etc) of news/research articles and clinical trials in order to measure the discrepancy between what is talked about in the media and what is being researched and tested in clinic.  It was interesting to hear that huge amounts of ink have been spilled on neurological disorders and the potential of stem cells to cure them (likely due to celebrity endorsement) compared to the cell types being used in clinical trials (mostly mesenchymal and blood stem cells). 

One question I’ve always had about such “expectation vs. reality” talks is why researchers never seem to quantify actual public expectations. In my own experience, it seems that outside of patients/families who are directly interested (and often desperate), the public has a pretty good understanding that scientific research takes a long time and are as concerned about safety as they are about speed -- could this be a case of the media hyping an “expectation hype” that isn’t actually present? I’d love to see the data on that or hear from blog readers.

 

Image: Patterns in Metamorphosis by Radha Chaddah. Showing at the Till and McCulloch Meetings, Montreal, April 30-May 2. Flourescent micrographs of differentiating neural stem cells on Masa paper, epoxy, aluminum wire, LED strips.

 

View from the floor 2: Till & McCulloch Meetings

Commercialization plenary summary, part 2 of 4

by Paul Krzyzanowski

One of the most dynamic speakers of the conference thus far was Greg Bonfiglio of Proteus Venture Partners. A well-known VC speaker in this area, Bonfiglio shared his perspectives of how the commercialization of regenerative medicine technologies, and of biotechnology in general, has evolved.

Proteus Venture Partners supports or invests in companies developing diverse products for the regenerative medicine market, ranging from ambitious cell based therapies or compounds that trigger endogenous regeneration, to tools such as cell and cell-based assays that are needed to advance discoveries in this field. 

Bonfiglio illustrated that the early days of regenerative medicine companies were tissue engineering companies, but that they came out under extremely different conditions in the 1990’s where the funding was relatively easy. Inflated expectations crashed along with the market around 1999, with the IT sector leading the drop. 

Investment in regenerative medicine seemed to have been triggered with the announcement of $3 billion to be deployed through the California Institute of Regenerative Medicine (CIRM). This also had the effect of stimulating other governments to contribute money to the field.

Today the situation is very different. “We’re seeing a significant volume of clinical trials” says Bonfiglio, “It’s indicative of a mature market.” He continued to show that dramatic revenue growth in cell therapies has been seen over the last few years. 

That’s especially impressive considering the economic crisis of the last few years, which Bonfiglio described as “the worst economic environment of the last 75 years.”

Any indications of success were tempered by warnings of significant challenges in the field, namely: standardization of cell lines, technologies for safe and reliable expansion of cells, methods to track cell migration & engraftment, and mechanisms for modulating immune function. Regulatory environments need to be updated and clarified as well.

Perhaps the most pressing technological need (reiterated later in the day by Stephen Minger) is to set rodent toxicology models aside. Bonfiglio emphatically stated that too many technologies fail today because successful results in rodent models don’t extend to humans.  

Some significant changes to biotech business models need to take place as well.

Bonfiglio painted the old, antiquated model of a pre-IPO company; one that would spend $90 million of precious start up funds to build a company that resembles a “miniature Johnson & Johnson”. The consequence is that most of investor funds would be spent on a façade (my word, not his!) that didn’t add any value to the underlying technology. 

“We’re in an industry that builds products that need to work”, said Bonfiglio. The new regenerative medicine model that’s taking hold is one of companies that are collaborative and capital efficient.  I presume the same applies to any biotech spinoff today.

“You definitely need to use [commercialization] centres to advance a virtual business -- [knowledge] translation centers that offer support like state-of-the-art facilities, GMP compliance, and access to deep knowledge of regenerative medicine at associated academic centers.”

On a more pragmatic note, Bonfiglio also warned everyone that the availability of funds has shrunk as venture capital risk tolerance has dropped.

The old model that investors went by assumed that the risks in new companies could be mitigated by bringing in experienced management, forging cross-company collaborations (i.e. to scale up industrial production of a biologic), or improving patent positions (i.e. by licensing some key technology that was lacking). Today, companies need to look nearly perfect. An abundance of preclinical data and successful Phase 1, if not Phase 2, clinical trials need to be completed before you can deal with most institutional investors.

This puts for-profit companies in the odd situation where the largest source of funding for commercialization comes from government and government-sponsored bodies, like CIRM. 

As industrial research seems to be moving back to quasi-academic settings, Bonfiglio ended on an upbeat note where collaboration is key and the idea of companies built within walls of patents and trade secrets is passé. “Don’t think of competitors as competitors.”  

“There is a false notion that the way to create and capture value in any industry is based on a [patenting] land-grab. There is little sense in fighting [with each other].  Our industry needs to settle disagreements without litigation.”

 

 

View from the floor 1: Till & McCulloch Meetings

Commercialization plenary summary, part 1 of 4

by Paul Krzyzanowski

Till and McCulloch Meeting (#TMM2012) attendees in Montreal had the opportunity to hear from four speakers involved in commercializing discoveries in regenerative medicine, from the perspectives of not-for-profit, financial and industrial organizations. I’ll separate these out into a few posts.

From Toronto’s Centre for the Commercialization of Regenerative Medicine, Dr. Michael May began today’s plenary by sharing a sincere assessment of the challenges faced by entrepreneurs and fledgling regenerative medicine companies in Canada. (I spoke with May late last year on the needs of Canadian startups in the biotech and regenerative medicine sectors.)

“Commercialization is very, very difficult … there are plenty of great ideas being developed, but [across Canada] there’s a lack of capital, universities have underused technology transfer offices, and we’ve seen premature company formation and licensing of technology to regions outside of the country.”

To counter these problems, May outlined plans at the CCRM to enable local start ups through the support of product development, the integration of scientific research and business, as well as industry engagement. A hallmark of the plan is product development core facilities, through which companies can eliminate the need to replicate common resources and instead focus their efforts on what’s valuable to startups: proving and developing their technologies. This is especially true for firms developing new methods of cell manufacturing, commercializing bioreactors, biosensors, biocompatible materials, and transplantable cells.

But perhaps the two hottest market needs identified by May, along with other presenters today, are well characterized human stem cell lines and the continued development of tissue mimetics for drug screening. 

“In just the last 10 months, we’ve evaluated 31 potential technologies and have formed 10 industry collaborations” says May, “We’ve also managed to generate revenues from iPS cell production”.  An industry consortium of 20 companies has also been formed, acting a proxy for the regenerative medicine industry. 

One of the highlights of May’s presentation was the report of an imminent spinoff in the next few months.  Contrary to common assumptions of startup, the company won’t be featuring a single lone researcher with a single concept: “[This company] involved technology from across Canada along with some international intellectual property.” 

It seems CCRM is developing a reputation as a successful technology broker.  May explained that CCRM also wants to play the role of a mentor or coach for researchers, and I think it’s fair to generalize that academic researchers seldom have the time to perform in-depth market research for commercializable products.

“We want to be internationally recognized as the leading global developer of regenerative medicine technology and patents,” said May. 

 

35 reasons to like stem cells

by Lisa Willemse

2010 Cells I See winner: The Beauty of Pluripotency by Kamal Garcha

For the past four years, the Stem Cell Network has held a small image/art contest, known as Cells I See. You may have viewed announcements of the winners in previous blog posts. The contest, by and large, was a quiet affair, known only to a few who weren't part of the Network's annual scientific conference -- where the entries were displayed and conference attendees selected the winner via blind judging.

We were content to keep it this way, until we realized that we were, in essence, hiding some of the most incredible stem cell images we've ever seen. Prompted by interest from the Ontario Science Centre, we installed a small exhibit in their museum and the response was incredible. Most people had no idea what stem cells looked like and were amazed at their beauty and complexity. The overriding message was that people are interested not just in the science of stem cells, but in stem cell images and art.

In response, Cells I See has gone social -- we've opened up the 2012 voting to the world. Anyone with a Facebook profile can participate by "liking" any of the 35 entries in this year's contest. Of course, we invite you to share it with your friends and colleagues as well -- the images are breathtaking, displaying a range of cell types, colours and patterns. 

But don't take my word for it, go see them for yourself. 

 

Another success for StemCellTalks

by Ben Paylor

Photo: Mario Moscovici

For those who have been involved with StemCellTalks, it’s hard to believe that it’s already in its third year. Some degree of perspective on the pace at which it has been growing can be found in the numbers associated with the event. To date, StemCellTalks symposia have been hosted six times in four different Canadian cities involving nearly a thousand high school students, hundreds of grad students and a growing list of prominent researchers. With a further two symposia planned for 2012 (Ottawa and Vancouver) and students mobilizing in new cities to expand the initiative, it’s clear that StemCellTalks is here to stay.