Tag Archives: stem cells

Targeted nanoparticles stimulate growth of healthy heart cells in damaged hearts

Don’t get too excited, the research is at the rat stage sometimes called ‘animal models’ as in ‘these nanoparticles are being tested on animal models’. Still it’s exciting news from North Carolina State University (NCSU; my second item from that university today, Sept. 12, 2014).

From a Sept. 12, 2014 news item on Azonano,

A targeted nanoparticle created by researchers at North Carolina State University and the Cedars-Sinai Heart Institute may help heart attack patients regenerate healthy heart tissue without using donated or processed stem cells. This new nanomedicine could also alleviate some of the difficulties involved with stem cell therapy, including treatment delays and invasive procedures.

A Sept. ?, 2014 NCSU news release, which originated the news item, provides a little more detail about the work,

The particle, a “magnetic bi-functional cell engager” called MagBICE, consists of an iron platform with two different antibodies attached. These antibodies have different functions – one locates a patient’s own stem cells after a heart attack, and the other grabs injured tissue, allowing MagBICE to act as a matchmaker between injury and repair crew. The iron platform makes MagBICE magnetically active, allowing physicians to direct the particles to the heart with an external magnetic field. The iron platform also enables magnetic resonance imaging (MRI).

Ke Cheng, associate professor of regenerative medicine at NC State, and his colleagues at Cedars-Sinai Heart Institute tested MagBICE in rats and found that the particle was effective in redirecting stem cells in the blood to the injured heart. [emphasis] Additionally, MagBICE was easier and faster to administer than current stem cell therapy products.

“MagBICE optimizes and amplifies the body’s own repair process, which means we don’t have to worry about patient rejection of donated stem cells, or delay treatment while a patient’s stem cells are being processed, purified and prepared,” Cheng says. “The drug can be offered to patients immediately after blood vessels to the damaged areas are reopened and can be given intravenously, which isn’t possible with stem cell therapy.”

Courtesy of NCSU, there’s an artist’s illustration of the MagBICE and the heart,

MagBICE engaging therapeutic stem cells with injured cardiomyocytes. Credit: Alice Harvey, NC State

MagBICE engaging therapeutic stem cells with injured cardiomyocytes. Credit: Alice Harvey, NC State

Here’s a link to and a citation for the paper,

Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting by Ke Cheng, Deliang Shen, M. Taylor Hensley, Ryan Middleton, Baiming Sun, Weixin Liu, Geoffrey De Couto, & Eduardo Marbán. Nature Communications 5, Article number: 4880 doi:10.1038/ncomms5880 Published 10 September 2014

This is an open access paper.

Growing new brain cells for implants

The dream is that one day this research will allow doctors to replace damaged or destroyed brain cells. According to the May 7, 2013 news release on EurekAlert,

A key type of human brain cell developed in the laboratory grows seamlessly when transplanted into the brains of mice, UC [University of California] San Francisco researchers have discovered, raising hope that these cells might one day be used to treat people with Parkinson’s disease, epilepsy, and possibly even Alzheimer’s disease, as well as and complications of spinal cord injury such as chronic pain and spasticity.

“We think this one type of cell may be useful in treating several types of neurodevelopmental and neurodegenerative disorders in a targeted way,” said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF [University of California San Francisco] and co-lead author on the paper.

The May 7, 2013 University of California San Francisco news release by Jeffrey Norris, which originated the release on EurekAlert, provides more detail about the work,

The researchers generated and transplanted a type of human nerve-cell progenitor called the medial ganglionic eminence (MGE) cell, in experiments described in the May 2 edition of Cell Stem Cell. Development of these human MGE cells within the mouse brain mimics what occurs in human development, they said.

To generate MGE cells in the lab, the researchers reliably directed the differentiation of human pluripotent stem cells — either human embryonic stem cells or induced pluripotent stem cells derived from human skin. These two kinds of stem cells have virtually unlimited potential to become any human cell type. When transplanted into a strain of mice that does not reject human tissue, the human MGE-like cells survived within the rodent forebrain, integrated into the brain by forming connections with rodent nerve cells, and matured into specialized subtypes of interneurons

The researchers are investigating applications other than brain cell replacement or repair (from the UCSF news release),

Previously, UCSF researchers led by Allan Basbaum, PhD, chair of anatomy at UCSF, have used mouse MGE cell transplantation into the mouse spinal cord to reduce neuropathic pain, a surprising application outside the brain. Kriegstein, Nicholas and colleagues now are exploring the use of human MGE cells in mouse models of neuropathic pain and spasticity, Parkinson’s disease and epilepsy.

“The hope is that we can deliver these cells to various places within the nervous system that have been overactive and that they will functionally integrate and provide regulated inhibition,” Nicholas said.

The researchers also plan to develop MGE cells from induced pluripotent stem cells derived from skin cells of individuals with autism, epilepsy, schizophrenia and Alzheimer’s disease, in order to investigate how the development and function of interneurons might become abnormal — creating a lab-dish model of disease.

There is at least one hurdle to be overcome (from the UCSF news release),

One mystery and challenge to both the clinical and pre-clinical study of human MGE cells is that they develop at a slower, human pace, reflecting an “intrinsic clock”. In fast-developing mice, the human MGE-like cells still took seven to nine months to form interneuron subtypes that normally are present near birth.

“If we could accelerate the clock in human cells, then that would be very encouraging for various applications,” Kriegstein said.

Here’s a link to and a citation for the researchers’ paper,

Functional Maturation of hPSC-Derived Forebrain Interneurons Requires an Extended Timeline and Mimics Human Neural Development by Cory R. Nicholas, Jiadong Chen, Yunshuo Tang, Derek G. Southwell, Nadine Chalmers, Daniel Vogt, Christine M. Arnold, Ying-Jiun J. Chen, Edouard G. Stanley, Andrew G. Elefanty, Yoshiki Sasai, Arturo Alvarez-Buylla, John L.R. Rubenstein, Arnold R. Kriegstein. Cell Stem Cell, Volume 12, Issue 5, 573-586, 2 May 2013

Copyright © 2013 Elsevier Inc. All rights reserved.
10.1016/j.stem.2013.04.005

This research put in me in mind of my Mar. 15, 2013 posting titled, Growing a tooth—as an adult, when I featured research at King’s College London where scientists had successfully used mouse stem cells to  grow teeth in adult mice. The researchers hope to one day be able to do the same in humans.

If vat-grown burgers are here, what are the social implications?

The Jan. 17, 2013 news item on Nanowerk about Dr. Neil Stephens and his research into the social implications of vat-grown (aka, in vitro meat) poses some interesting questions,

he [sic] world’s first laboratory-grown hamburger has been produced by Professor Mark Post and his team in Maastricht, representing something radically new in our world. Dr Neil Stephens, Research Associate at Cesagen (Cardiff School of Social Sciences), has been researching the social and ethical issues of this technology and what this innovation in stem cell science might mean for us in 2013.

Will we be eating burgers made in test-tubes in the near future? That is probably unlikely considering Professor Post’s burger costs around £200,000 to produce.

The University of Cardiff Jan. 16, 2013 news release,which originated the news item, goes on to explain why Stephens is conducting this investigation,

However, the benefits this new technology can deliver – according to the scientists – include slaughter-free meat that is healthier and free from animal to human disease. The meat could also be grown during space travel and could have a much smaller environmental impact than today’s whole-animal reared meat. But it is not yet clear if any of these can be delivered in a marketable form.

Since 2008, Dr Stephens has been investigating these ‘social promises’ by interviewing most of the scientists across the world who are involved in this project. He looks to understand how this community of scientists came together and what strategies they use to justify the promises they make.

Professor Mark Post’s work at the University of Maastricht (Holland) was covered extensively last year when it was presented at the 2012 AAAS (American Ass0ciation for the Advancement of Science) meeting in Vancouver. This Feb. 19, 2012 article by Pallab Ghosh for BBC (British Broadcasting Corporation) online highlights some of the discussion which took place then,

Dutch scientists have used stem cells to create strips of muscle tissue with the aim of producing the first lab-grown hamburger later this year.

The aim of the research is to develop a more efficient way of producing meat than rearing animals.

Professor Post’s group at Maastricht University in the Netherlands has grown small pieces of muscle about 2cm long, 1cm wide and about a mm thick.

They are off-white and resemble strips of calamari in appearance. These strips will be mixed with blood and artificially grown fat to produce a hamburger by the autumn [2012].

…Some estimate that food production will have to double within the next 50 years to meet the requirements of a growing population. During this period, climate change, water shortages and greater urbanisation will make it more difficult to produce food.

Prof Sean Smukler from the University of British Columbia said keeping pace with demand for meat from Asia and Africa will be particularly hard as demand from these regions will shoot up as living standards rise. He thinks that lab grown meat could be a good solution.

But David Steele, who is president of Earthsave Canada, said that the same benefits could be achieved if people ate less meat.

“While I do think that there are definite environmental and animal welfare advantages of this high-tech approach over factory farming, especially, it is pretty clear to me that plant-based alternatives… have substantial environmental and probably animal welfare advantages over synthetic meat,” he said.

Dr Steele, who is also a molecular biologist, said he was also concerned that unhealthily high levels of antibiotics and antifungal chemicals would be needed to stop the synthetic meat from rotting.

There doesn’t seem to be any more recent news about vat-grown meat from Post’s team at the University of Maastricht; the interest in Stephens’ sociological work on the topic seems to have been stimulated by his inclusion in the UK’s Economic and Social Research Council’s (ESRC) annual publication, (Britain in magazine) Britain in 2013.

Here’s more about Stephens’ and his sociological inquiry,

Squishy knees and tissue engineering at Johns Hopkins

Researchers at Johns Hopkins University School of Medicine’s Translational Tissue Engineering Center (TTEC) have developed a material (a kind of hydrogel) which they use with a new technique they’ve developed for growing new tissue and cartilage in knees. From the Jan. 15, 2013 news release on EurekAlert,

Proof-of-concept clinical trial in 18 patients shows improved tissue growth

In a small study, researchers reported increased healthy tissue growth after surgical repair of damaged cartilage if they put a “hydrogel” scaffolding into the wound to support and nourish the healing process. The squishy hydrogel material was implanted in 15 patients during standard microfracture surgery, in which tiny holes are punched in a bone near the injured cartilage. The holes stimulate patients’ own specialized stem cells to emerge from bone marrow and grow new cartilage atop the bone.

“Our pilot study indicates that the new implant works as well in patients as it does in the lab, so we hope it will become a routine part of care and improve healing,” says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Johns Hopkins University School of Medicine’s Translational Tissue Engineering Center (TTEC). Damage to cartilage, the tough-yet-flexible material that gives shape to ears and noses and lines the surface of joints so they can move easily, can be caused by injury, disease or faulty genes. Microfracture is a standard of care for cartilage repair, but for holes in cartilage caused by injury, it often either fails to stimulate new cartilage growth or grows cartilage that is less hardy than the original tissue.

Here are more details from the Johns Hopkins Jan. 15, 2013 news release,

Tissue engineering researchers, including Elisseeff, theorized that the specialized stem cells needed a nourishing scaffold on which to grow, but demonstrating the clinical value of hydrogels has “taken a lot of time,” Elisseeff says. By experimenting with various materials, her group eventually developed a promising hydrogel, and then an adhesive that could bind it to the bone.

After testing the combination for several years in the lab and in goats, with promising results, she says, the group and their surgeon collaborators conducted their first clinical study, in which 15 patients with holes in the cartilage of their knees received a hydrogel and adhesive implant along with microfracture. For comparative purposes, another three patients were treated with microfracture alone. After six months, the researchers reported that the implants had caused no major problems, and MRIs showed that patients with implants had new cartilage filling an average 86 percent of the defect in their knees, while patients with only microfracture had an average of 64 percent of the tissue replaced. Patients with the implant also reported a greater decrease in knee pain in the six months following surgery, according to the investigators.

The trial continues, has enrolled more patients and is now being managed by a company called Biomet. The trial is part of efforts to win European regulatory approval for the device.

In the meantime, Elisseeff says her team has begun developing a next-generation implant, one in which the hydrogel and adhesive will be combined in a single material. In addition, they are working on technologies to lubricate joints and reduce inflammation.

The study has been published in the AAAS’s (American Association for the Advancement of Science) Science Translational Medicine journal,

Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite

Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel

Sci Transl Med 9 January 2013:
Vol. 5 no. 167 pp. 167ra6DOI:10.1126/scitranslmed.3004838

This article is behind a paywall and for some reason the authors are listed only in the news release,

Jennifer Elisseeff, Blanka Sharma, Sara Fermanian, Matthew Gibson, Shimon Unterman, Daniel A. Herzka, Jeannine Coburn and Alexander Y. Hui of the Johns Hopkins School of Medicine; Brett Cascio of Lake Charles Memorial Hospital; Norman Marcus, a private practice orthopedic surgeon; and Garry E. Gold of Stanford University

The State of Science and Technology in Canada, 2012 report—examined (part 2: the rest of the report)

The critiques I offered in relation to the report’s  executive summary (written in early Oct. 2012 but not published ’til now) and other materials can remain more or less intact now that I’ve read the rest of the report (State of Science and Technology in Canada, 2012 [link to full PDF report]). Overall, I think it’s a useful and good report despite what I consider to be some significant shortcomings, not least of which is the uncritical acceptance of the view Canada doesn’t patent enough of its science and its copyright laws are insufficient.

My concern regarding the technometrics (counting patents) is definitely not echoed in the report,

One key weakness of these measures is that not all types of technology development lead to patentable technologies. Some, such as software development, are typically subject to copyright instead. This is particularly relevant for research fields where software development may be a key aspect of developing new technologies such as computer sciences or digital media. Even when patenting is applicable as a means of commercializing and protecting intellectual property (IP), not all inventions are patented. (p. 18 print, p. 42 PDF)

In my view this is a little bit like fussing over the electrical wiring when the foundations of your house are  in such bad repair that the whole structure is in imminent danger of falling. As noted in my critique of the executive summary, the patent system in the US and elsewhere is in deep, deep trouble and, is in fact, hindering innovation. Here’s an interesting comment about patent issues being covered in the media (from a Dec. 27, 2012 posting by Mike Masnick for Techdirt),

There’s been a recent uptick in stories about patent trolling getting mainstream media attention, and the latest example is a recent segment on CBS’s national morning program, CBS This Morning, which explored how patent trolls are hurting the US economy …

… After the segment, done by Jeff Glor, one of the anchors specifically says to him [Austin Meyer of the Laminer company which is fighting a patent troll in court and getting coverage on the morning news]: “So it sounds like this is really stifling innovation and it hurts small businesses!”

Getting back to the report, I’m in more sympathy with the panel’s use of  bibliometrics,

As a mode of research assessment, bibliometric analysis has several important advantages. First, these techniques are built on a well-developed foundation of quantitative data. Publication in peer-reviewed journals is a cornerstone of research dissemination in most scientific and academic disciplines, and bibliometric data are therefore one of the few readily available sources of quantitative information on research activity that allow for comparisons across many fields of research. Second, bibliometric analyses are able to provide information about both research productivity (i.e., the quantity of journal articles produced) and research impact (measured through citations). While there are important methodological issues associated with these metrics (e.g., database coverage by discipline, correct procedures for normalization and aggregation, self-citations, and negative citations, etc.), [emphasis mine] most bibliometric experts agree that, when used appropriately, citation based indicators can be valid measures of the degree to which research has had an impact on later scientific work … (p. 15 print, p. 39, PDF)

Still, I do think that a positive publication bias (i.e., the tendency to publish positive results over negative or inclusive results) in the field medical research should have been mentioned as it is a major area of concern in the use  of bibliometrics and especially since one of the identified areas of  Canadian excellence is  in the field of medical research.

The report’s critique of the opinion surveys has to be the least sophisticated in the entire report,

There are limitations related to the use of opinion surveys generally. The most important of these is simply that their results are, in the end, based entirely on the opinions of those surveyed. (p. 20 print, p. 44 PDF)

Let’s see if I’ve got this right. Counting the number of citations a paper, which was peer-reviewed (i.e., a set of experts were asked for their opinions about the paper prior to publication) and which may have been published due to a positive publication, bias yields data (bibliometrics) which are by definition more reliable than an opinion. In short, the Holy Grail (a sacred object in Christian traditions) is data even though that data or ‘evidence’  is provably based on and biased by opinion which the report writers identify as a limitation. Talk about a conundrum.

Sadly the humanities, arts, and social sciences (but especially humanities and arts) posed quite the problem regarding evidence-based analysis,

While the Panel believes that most other evidence-gathering activities undertaken for this assessment are equally valid across all fields, the limitations of bibliometrics led the Panel to seek measures of the impact of HASS [Humanities, Arts, and Social Sciences] research that would be equivalent to the use of bibliometrics, and would measure knowledge dissemination by books, book chapters, international awards, exhibitions, and other arts productions (e.g., theatre, cinema, etc.). Despite considerable efforts to collect information, however, the Panel found the data to be sparse and methods to collect it unreliable, such that it was not possible to draw conclusions from the resulting data. In short, the available data for HASS-specific outputs did not match the quality and rigour of the other evidence collected for this report. As a result, this evidence was not used in the Panel’s deliberations.

Interestingly, the expert panel was led by Dr. Eliot Phillipson, Sir John and Lady Eaton Professor of Medicine Emeritus, [emphasis mine] University of Toronto, who received his MD in 1963. Evidence-based medicine is the ne plus ultra of medical publishing these days. Is this deep distress over a lack of evidence/data in other fields a reflection of the chair’s biases?  In all the discussion and critique of the methodologies, there was no discussion about reflexivity, i. e., the researcher’s or, in this case, the individual panel members’ (individually or collectively) biases and their possible impact on the report. Even with so called evidence-based medicine, bias and opinion are issues.

While the panel was not tasked to look into business-led R&D efforts (there is a forthcoming assessment focused on that question) mention was made in Chapter 3 (Research Investment) of the report. I was particularly pleased to see mention of the now defunct Nortel with its important century long contribution to Canadian R&D efforts. [Full disclosure: I did contract work for Nortel on and off for two years.]

A closer look at recent R&D expenditure trends shows that Canada’s total investment in R&D has declined in real terms between 2006 and 2010, driven mainly by declining private-sector research performance. Both government and higher education R&D expenditures increased modestly over the same five-year period (growing by 4.5 per cent and 7.1 per cent respectively), while business R&D declined by 17 per cent (see Figure 3.3). Much of this decline can be attributed to the failing fortunes and bankruptcy of Nortel Networks Corporation, which was one of Canada’s top corporate R&D spenders for many years. Between 2008 and 2009 alone, global R&D expenditure at Nortel dropped by 48 per cent, from nearly $1.7 billion to approximately $865 million (Re$earch Infosource, 2010) with significant impact on Canada. Although growth in R&D expenditure at other Canadian companies, particularly Research In Motion, partially compensated for the decline at Nortel, the overall downward trend remains. (p. 30 print, p. 54 PDF)

Chapter 4 of the report (Research Productivity and Impact) is filled with colourful tables and various diagrams and charts illustrating areas of strength and weakness within the Canadian research endeavour, my concerns over the metrics notwithstanding. I was a bit startled by our strength in Philosophy and Theology (Table 4.2 on p. 41 print, p. 65 PDF) as it was not touted in the initial publicity about the report. Of course, they can’t mention everything so there are some other pleasant surprises in here. Going in the other direction, I’m a little disturbed by the drop (down from 1.32 in 1999-2004 to 1.12 in 2005-1010) in the ICT (Information and Communication Technologies) specialization index but that is, as the report notes, a consequence of the Nortel loss and ICT scores better in other measures.

I very much appreciated the inclusion of the questions used in the surveys and the order in which they were asked, a practice which seems to be disappearing elsewhere. The discussion about possible biases and how the data was weighted to account for biases is interesting,

Because the responding population was significantly different than the sample population (p<0.01) for some countries, the data were weighted to correct for over- or under-representation. For example, Canadians accounted for 4.4 per cent of top-cited researchers, but 7.0 per cent of those that responded. After weighting, Canadians account for 4.4 per cent in the analyses that follow. This weighting changed overall results of how many people ranked each country in the top five by less than one per cent.

Even with weighting to remove bias in choice to respond, there could be a perception that self-selection is responsible for some results. Top-cited Canadian researchers in the population sample were not excluded from the survey but the results for Canada cannot be explained by self-promotion since 37 per cent of all respondents identified Canada among the top five countries in their field, but only 7 per cent (4.4 per cent after weighting) of respondents were from Canada. Similarly, 94 per cent of respondents identified the United States as a top country in their field, yet only 33 per cent (41 per cent after weighting) were from the United States. Furthermore, only 9 per cent of respondents had either worked or studied in Canada, and 28 per cent had no personal experience of, or association with, Canada or Canadian researchers (see Table 5.2). It is reasonable to conclude that the vast majority of respondents based their evaluation of Canadian S&T on its scientific contributions and reputation alone. (p. 65 print, p. 89 PDF)

There is another possible bias  not mentioned in the report and that has to do with answering the question: What do you think my strengths and weaknesses are? If somebody asks you that question and you are replying directly, you are likely to focus on their strong points and be as gentle as possible about their weaknesses. Perhaps the panel should consider having another country ask those questions about Canadian research. We might find the conversation becomes a little more forthright and critical.

Chapter 6 of the report discusses research collaboration which is acknowledged as poorly served by bibliometrics. Of course, collaboration is a strategy which Canadians have succeeded with not least because we simply don’t have the resources to go it alone.

One of the features I quite enjoyed in this report are the spotlight features. For example, there’s the one on stem cell research,

Spotlight on Canadian Stem Cell Research

Stem cells were discovered by two Canadian researchers, Dr. James Till and the late Dr. Ernest McCulloch, at the University of Toronto over 50 years ago. This great Canadian contribution to medicine laid the foundation for all stem cell research, and put Canada firmly at the forefront of this field, an international leadership position that is still maintained.

Stem cell research, which is increasingly important to the future of cell replacement therapy for diseased or damaged tissues, spans many disciplines. These disciplines include biology, genetics, bioengineering, social sciences, ethics and law, chemical biology, and bioinformatics. The research aims to understand the mechanisms that govern stem cell behaviour, particularly as it relates to disease development and ultimately treatments or cures.

Stem cell researchers in Canada have a strong history of collaboration that has been supported and strengthened since 2001 by the Stem Cell Network (SCN) (one of the federal Networks of Centres of Excellence), a network considered to be a world leader in the field. Grants awarded through the SCN alone have affected the work of more than 125 principal investigators working in 30 institutions from Halifax to Vancouver. Particularly noteworthy institutions include the Terry Fox Laboratory at the BC Cancer Agency; the Hotchkiss Brain Institute in Calgary; Toronto’s Hospital for Sick Children, Mount Sinai Hospital, University Health Network, and the University of Toronto; the Sprott Centre for Stem Cell Research in Ottawa; and the Institute for Research in Immunology and Cancer in Montréal. In 2010, a new Centre for the Commercialization of Regenerative Medicine was formed to further support stem cell initiatives of interest to industry partners.

Today, Canadian researchers are among the most influential in the stem cell and regenerative medicine field. SCN investigators have published nearly 1,000 papers since 2001 in areas such as cancer stem cells; the endogenous repair of heart, muscle, and neural systems; the expansion of blood stem cells for the treatment of a variety of blood-borne diseases; the development of biomaterials for the delivery and support of cellular structures to replace damaged tissues; the direct conversion of skin stem cells to blood; the evolutionary analysis of leukemia stem cells; the identification of pancreatic stem cells; and the isolation of multipotent blood stem cells capable of forming all cells in the human blood system. (p. 96 print, p. 120 PDF)

Getting back to the report and my concerns, Chapter 8 on S&T capacity focuses on science training and education,

• From 2005 to 2009, there were increases in the number of students graduating from Canadian universities at the college, undergraduate, master’s and doctoral levels, with the largest increase at the doctoral level.

• Canada ranks first in the world for its share of population with post-secondary education.

• International students comprise 11 per cent of doctoral students graduating from Canadian universities. The fields with the largest proportions of international students include Earth and Environmental Sciences; Mathematics and Statistics; Agriculture, Fisheries, and Forestry; and Physics and Astronomy.

• From 1997 to 2010, Canada experienced a positive migration flow of researchers, particularly in the fields of Clinical Medicine, Information and Communication Technologies (ICT), Engineering, and Chemistry. Based on Average Relative Citations, the quality of researchers emigrating and immigrating was comparable.

• In three-quarters of fields, the majority of top-cited researchers surveyed thought Canada has world-leading research infrastructure or programs. (p. 118 print, p. 142 PDF)

Getting back to more critical matters, I don’t see a reference to jobs in this report. It’s all very well to graduate a large number of science PhDs, which we do,  but what’s the point if they can’t find work?

  • From 2005 to 2009, there were increases in the number of students graduating from Canadian universities at the college, undergraduate, master’s and doctoral levels, with the largest increase at the doctoral level.
  • Canada ranks first in the world for its share of population with post-secondary education.
  • International students comprise 11 per cent of doctoral students graduating from Canadian universities. The fields with the largest proportions of international students include Earth and Environmental Sciences; Mathematics and Statistics; Agriculture, Fisheries, and Forestry; and Physics and Astronomy.
  • From 1997 to 2010, Canada experienced a positive migration flow of researchers, particularly in the fields of Clinical Medicine, Information and Communication Technologies (ICT), Engineering, and Chemistry. Based on Average Relative Citations, the quality of researchers emigrating and immigrating was comparable.
  • In three-quarters of fields, the majority of top-cited researchers surveyed thought Canada has world-leading research infrastructure or programs. (p. 118 print, p. 142 PDF)

The Black Whole blog on the University Affairs website has discussed and continues to discuss the dearth of jobs in Canada for science graduates.

Chapter 9 of the report breaks down the information on a regional (provincial) bases. As you might expect, the research powerhouses are Ontario, Québec, Alberta and BC. Chapter 10 summarizes the material on a field basis, i.e., Biology; Chemistry; Agriculture, Fisheries, and Forestry; Econ0mics; Social Sciences; etc.  and those results were widely discussed at the time and are mentioned in part 1 of this commentary.

One of the most striking results in the report is Chapter 11: Conclusions,

The geographic distribution of the six fields of strength is difficult to determine with precision because of the diminished reliability of data below the national level, and the vastly different size of the research enterprise in each province.

The most reliable data that are independent of size are provincial ARC scores. Using this metric, the leading provinces in each field are as follows:

  • Clinical Medicine: Ontario, Quebec, British Columbia, Alberta
  • Historical Studies: New Brunswick, Ontario, British Columbia
  • ICT: British Columbia, Ontario
  •  Physics and Astronomy: British Columbia, Alberta, Ontario, Quebec
  • Psychology and Cognitive Sciences: British Columbia, Nova Scotia, Ontario
  • Visual and Performing Arts: Quebec [emphasis mine] (p. 193 print, p. 217 PDF)

Canada has an international reputation in visual and performing which is driven by one province alone.

As for our national fading reputation in natural resources and environmental S&T that seems predictable by almost any informed observer given funding decisions over the last several years.

The report does identify some emerging strengths,

Although robust methods of identifying emerging areas of S&T are still in their infancy, the Panel used new bibliometric techniques to identify research clusters and their rates of growth. Rapidly emerging research clusters in Canada have keywords relating, most notably, to:

• wireless technologies and networking,

• information processing and computation,

• nanotechnologies and carbon nanotubes, and

• digital media technologies.

The Survey of Canadian S&T Experts pointed to personalized medicine and health care, several energy technologies, tissue engineering, and digital media as areas in which Canada is well placed to become a global leader in development and application. (p. 195 print; p. 219 PDF)

I wish I was better and faster at crunching numbers because I’d like to spend time examining the data more closely but the reality is that all data is imperfect so this report like any snapshot is an approximation. Still, I would have liked to have seen some mention of changing practices in science. For example, there’s the protein-folding game, Foldit, which has attracted over 50,000 players (citizen scientists) who have answered questions and posed possibilities that had not occurred to scientists. Whether this trend will continue to disappear is to be answered in the future. What I find disconcerting is how thoroughly this and other shifting practices (scientists publishing research in blogs) and thorny issues such as the highly problematic patent system were ignored. Individual panel members or the report writers themselves may have wanted to include some mention but we’ll never know because the report is presented as a singular, united authority.

In any event, Bravo! to the expert panel and their support team as this can’t have been an easy job.

If you have anything to say about this commentary or the report please do comment, I would love to hear more opinions.

My carbon nanotube heart and patents

The stem cell scientists at the National University of Ireland (NUI) and Trinity College Dublin’s CRANN (Centre for Research on Adaptive Nanostructures and Nanodevices) aren’t making hearts out of carbon nanotubes but they are using the particles to stimulate stem cells into becoming heart-like.The Sept. 19, 2012 news item on Nanowerk provides context for this work,

Stem cell scientists have capitalised on the electrical properties of a widely used nanomaterial to develop cells which may allow the regeneration of cardiac cells. The breakthrough has been led by a team of scientists at the Regenerative Medicine Institute (REMEDI) at the National University of Ireland Galway in conjunction with Trinity College Dublin.

Heart disease is the leading cause of death in Ireland. Once damaged by heart attack, cardiac muscle has very little capacity for self-repair and at present there are no clinical treatments available to repair damaged cardiac muscle tissue.

Over the last 10 years, there has been tremendous interest in developing a cell-based therapy to address this problem. Since the use of a patient’s own heart cells is not a viable clinical option, many researchers are working to try to find an alternative source of cells that could be used for cardiac tissue repair.

The NUI Sept. 19, 2012 news release, which originated the news item, describes how carbon nanotubes have properties similar to certain heart cells and how the researchers decided to exploit that similarity,

The researchers recognised that carbon nanotubes, a widely used nanoparticle, is reactive to electrical stimulation. They then used these nanomaterials to create cells with the characteristics of cardiac progenitors, a special type of cell found in the heart, from adult stem cells.

“The electrical properties of the nanomaterial triggered a response in the mesenchymal (adult) stem cells, which we sourced from human bone marrow. In effect, they became electrified, which made them morph into more cardiac-like cells”, explains Valerie Barron of REMEDI at National University of Ireland Galway. “This is a totally new approach and provides a ready-source of tailored cells, which have the potential to be used as a new clinical therapy. Excitingly, this symbiotic strategy lays the foundation stone for other electroactive tissue repair applications, and can be readily exploited for other clinically challenging areas such as in the brain and the spinal cord.”

The team’s collaborator at CRANN, Professor Werner Blau made a comment I found a bit odd (from the NUI news release),

“It is great to see two decades of our pioneering nanocarbon research here at TCD come to fruition in a way that addresses a major global health problem. Hopefully many people around the world will ultimately benefit from it. Some of our carbon nanotube research has been patented by TCD and is being licensed to international companies in material science, electronics and health care,” said Professor Blau.

I’m not a big fan of the current patenting regimes which seem to  have been turned  into innovation-killing machines.  As for patenting medicines and medical devices, I recall that Frederick Banting and Charles Best who discovered insulin refused to patent the discovery as they believed it would constrain access.

I appreciate that businesses need to make money and scientists need money to do their work and so on but this blind rush to patent discoveries seems a little misguided to me and it might be a good time to consider new business and economic models.

Speeding up bone growth with a tobacco virus

Steven Powell in a June 22, 2012 article for the University of South Carolina news office describes progress that Qian Wang, a chemistry professor, and his colleagues at the University of South Carolina have made toward cutting down the time it takes to heal a bone. From the June 22, 2012 article (Note: I have removed a link),

Wang, Andrew Lee and co-workers just reported in Molecular Pharmaceutics that surfaces coated with bionanoparticles could greatly accelerate the early phases of bone growth. Their coatings, based in part on genetically modified Tobacco mosaic virus, reduced the amount of time it took to convert stem cells into bone nodules – from two weeks to just two days.

Here’s a description of the healing process,

The human body continuously generates and circulates cells that are undifferentiated; that is, they can be converted into the components of a range of tissues, such as skin or muscle or bone, depending on what the body needs.

The conversion of these cells – called stem cells – is set into motion by external cues. In bone healing, the body senses the break at the cellular level and begins converting stem cells into new bone cells at the location of the break, bonding the fracture back into a single unit.

There are reasons for wanting to speed the process,

The process is very slow, which is helpful in allowing a fracture to be properly set, but after that point the wait is at least an inconvenience, and in some cases highly detrimental.

“With a broken femur, a leg, you can be really incapacitated for a long time,” said Wang. “In cases like that, they sometimes inject a protein-based drug, BMP-2, which is very effective in speeding up the healing process. Unfortunately, it’s very expensive and can also have some side effects.”

Wang and his colleagues stumbled across a new approach to speeding up the healing process (Note: I have removed a link),

In a search for alternatives four years ago, Wang and colleagues uncovered some unexpected accelerants of bone growth: plant viruses. They originally meant for these viruses, which are harmless to humans, to work as controls. They coated glass surfaces with uniform coverings of the Turnip yellow mosaic virus and Tobacco mosaic virus, originally intending to use them as starting points for examining other potential variations.

But they were surprised to find that the coatings alone could reduce the amount of time to grow bone nodules from stem cells. Since then, Wang and co-workers have refined their approach to better define just what it is that accelerates bone growth.

This is a description of their latest refinements and what they imagine to be possible at some time in the future,

In the most recent effort spearheaded by Lee, they built up a layer-by-layer assembly underneath the virus coating to ensure stability. They also genetically modified the viral protein to enhance the interaction between the coating and the stem cells and help drive them toward bone growth.

Their efforts were rewarded with bone nodules that formed just two days after the addition of stem cells, compared to two weeks with a standard glass surface. They’re also carefully following the cellular signs involved with success. BMP-2 is involved, but as an intrinsic cellular product rather than an added drug.

“BMP-2 is bone morphogenetic protein 2. It can be added as a protein-based drug, but it’s a natural protein produced in the cell,” said Wang. “We see upregulation of the BMP-2 within 8 hours with the new scaffold.” They also find osteocalcin expression and calcium sequestration, two processes associated with bone formation, to be much more pronounced with their new coatings.

“What we’ve seen could prove very useful, particularly when it comes to external implants in bones,” said Wang. “With those, you have to add a foreign material, and knowing that a coating might increase the bone growth process is clearly beneficial.”

“But more importantly, we feel we’re making progress in a more general sense in bone engineering. We’re really showing the direct correlation between nanotopography and cellular response. If our results can be further developed, in the future you could use titanium to replace the bone, and you might be able to use different kinds of nanoscale patterning on the titanium surface to create all kinds of different cellular responses.” [emphasis mine]

I had not expected to leap from bone tissue engineering to creating titanium bones  the sort of thing that I imagine much interests the military.  As for “different cellular responses,” my imagination fails. What is being suggested? Thanks to the June 25,2012 news item on Nanowerk for alerting me to this work.

Body parts nano style

In early July 2011, there were reports of a new kind of transplant involving a body part made of a biocomposite. Andemariam Teklesenbet Beyene underwent a trachea transplant that required an artificial windpipe crafted by UK experts then flown to Sweden where Beyene’s stem cells were used to coat the windpipe before being transplanted into his body.

It is an extraordinary story not least because Beyene, a patient in a Swedish hospital planning to return to Eritrea after his PhD studies in Iceland, illustrates the international cooperation that made the transplant possible.

The scaffolding material for the artificial windpipe was developed by Professor Alex Seifalian at the University College London in a landmark piece of nanotechnology-enabled tissue engineering. Tim Harper in his July 25, 2011 posting provides more details about the scaffolding,

A team led by Professor Alexander Seifalian (UCL Division of Surgery & Interventional Science; professor of nanotechnology and regenerative medicine at University College London, UK), whose laboratories are headquartered at the Royal Free Hospital, created a glass mold of the patient’s trachea from X-ray computed tomography (CT) scans of the patient. In CT, digital geometry processing is employed to generate a 3D image of the inside of an object from a large series of 2D X-ray images taken around one single axis of rotation.

Then, they manufactured a full size y-shaped trachea scaffold at Professor Seifalian’s laboratories. The scaffold of the trachea was built using a novel nanocomposite polymer developed and patented by Professor Seifalian. Professor Seifalian worked together with Professor Paolo Macchiarini at Karolinska Institutet, Stockholm, Sweden (who also holds an Honorary appointment at UCL).

Professor Seifalian and his team used a porous novel nanocomposite polymer to build the y-shaped trachea scaffold. The pores were millions of little holes, providing this way a place for the patient’s stem cells to grow roots. The team cut strips of the novel nanocomposite polymer and wrapped them around the glass mold creating this way the cartilage rings that conferred structural strength to the trachea.

After the scaffold construct was finished, it was taken to Karolinska Institutet where the patient’s stem cells were seeded by Professor Macchiarini’s team.

Harper goes on to provide more details and insight into what makes this event such an important one.

Meanwhile, Dexter Johnson’s (Nanoclast blog in the IEEE website) July 21, 2011 posting poses a question,

While the nanocomposite scaffold is a critical element to the artificial organ, perhaps no less important was the bioreactor used to grow the stem cells onto it, which was developed at Harvard Bioscience.

If you needed any evidence of how nanotechnology is not only interdisciplinary, but also international, you could just cite this case: UK-developed nanocomposite for the scaffolding material, US-based bioreactor in which the stem cells were grown onto the scaffolding and a Swedish-based medical institute to perform the transplant.

So I ask, which country or region is going to get rich from the breakthrough?

It’s an interesting question and I don’t think I would have framed it in quite that fashion largely because I don’t tend to think of countries or regions getting wealthy from biomedical products since pharmaceutical companies tend to be internationally based. Is Switzerland richer for Novartis?

I suppose I’m a product of the Canadian landscape from which I spring so I think of trees and mines as making a country or region richer as they are inextricably linked to their environment but pharmaceuticals or biomedical appliances can be manufactured anywhere. Consequently, a synthetic organ could be manufactured anywhere once the technology becomes easily available. Who gets rich from this development? I suspect that will be a person or persons if anyone but, not a region or a country.

Getting back to Beyene, here are more details from the July 7, 2011 BBC News article by Michelle Roberts,

Dr Alex Seifalian and his team used this fragile structure [the scaffold] to create a replacement for the patient, whose own windpipe was ravaged by an inoperable tumour.

Despite aggressive chemotherapy and radiotherapy, the cancer had grown to the size of a golf ball and was blocking his breathing. Without a transplant he would have died.

During a 12-hour operation Professor Macchiarini removed all of the tumour and the diseased windpipe and replaced it with the tailor-made replica [now covered with tissue grown from the patient's bone marrow tricked into growing like cells found in a trachea].

And, importantly, Mr Beyene’s body will accept it as its own, meaning he will not need to take the strong anti-rejection drugs that other transplant patients have to.

Professor Macchiarini said this was the real breakthrough.

“Thanks to nanotechnology, this new branch of regenerative medicine, we are now able to produce a custom-made windpipe within two days or one week.

“This is a synthetic windpipe. The beauty of this is you can have it immediately. There is no delay. This technique does not rely on a human donation.”

He said many other organs could be repaired or replaced in the same way.

A month on from his operation, Mr Beyene is still looking weak, but well.

Sitting up in his hospital bed, he said: “I was very scared, very scared about the operation. But it was live or die.”

My best wishes to Beyene and his family who are also pioneers.

 

Tony Clement announces Canadian government nano investment in two Alberta firms

Tony Clement, Canada’s Minister of Industry, announced investments totaling over $500,000 to two Alberta-based firms associated with nanotechnology. From the news release on Marketwire [ETA Aug.18.10: there's also this link to the item on Nanowerk],

The Honourable Tony Clement, Minister of Industry, today announced contributions of $285,268 to Sonoro Energy Limited and $257,000 to IntelligentNano Incorporated from the National Research Council of Canada Industrial Research Assistance Program (NRC-IRAP). The funding supports innovative research and development projects that will assist both firms in developing high-tech solutions for global markets.

“Our government is investing in science and technology to create good jobs, strengthen the economy and improve the quality of life of Canadians,” said Minister Clement. “This government is supporting Canadian firms that successfully develop and apply innovative technologies. Canada’s Economic Action Plan is bolstering scientific research and commercialization, while creating good jobs and economic growth.”

Edmonton boasts Canada’s largest and most technologically advanced nanotechnology research infrastructure, centred around the National Institute of Nanotechnology (NINT). NINT is a joint initiative between the National Research Council of Canada, the University of Alberta, and the Government of Alberta.

So there you have it, the follow up to yesterday’s news flash. If you’re curious about the two companies, Sonoro is using the money to,

[support] a project that will seek to accelerate the commercial upgrading of heavy oil into synthetic crude, by small and medium- sized producers in remote areas. As the technology is both scalable and repeatable, Sonoro is actively pursuing heavy oil resource opportunities, particularly in remote global regions where there is heavy oil that could benefit from low-cost upgrading technology. Sonoro Energy has developed and patented a proprietary sonic reactor technology platform that transfers sonic energy on an industrial scale to physical, chemical or biological processes.

IntelligentNano will apply its funds towards,

further development of the “Sonacell,” a device for amplifying and accelerating the growth of therapeutic stem cells. Stem cells have an ability to self-renew and the potential to replace diseased and damaged tissues in the body, without the risk of rejection and side effects. Adults have a very small number of such cells; IntelligentNano has developed the “Sonacell,” which will make it possible to harvest and grow a sufficient quantity of a patient’s own stem cells for use in medical therapies. The “Sonacell” opens the door to the possibility of treatments for diseases like diabetes, arthritis, Parkinson’s and spinal cord injuries.