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Real-time MRI for precise and predictable intra-arterial stem cell delivery to the central nervous system
An MRI shows stem cells labeled with iron oxide nanoparticles being injected into an animal’s brain. Click to view video. (Credit: Piotr Walczak/Johns Hopkins Medicine)
Working with animals, a team of scientists reports it has delivered stem cells to the brain with unprecedented precision by threading a catheter through an artery and infusing the cells under real-time MRI guidance.
In a description of the work, published online Sept. 12 in the Journal of Cerebral Blood Flow and Metabolism, they express hope that the tests in anesthetized dogs and pigs are a step toward human trials of a technique to treat Parkinson’s disease, stroke, and other brain damaging disorders.
“Although stem cell-based therapies seem very promising, we’ve seen many clinical trials fail. In our view, what’s needed are tools to precisely target and deliver stem cells to larger areas of the brain,” says Piotr Walczak, M.D., Ph.D., associate professor of radiology at the Johns Hopkins University School of Medicine’s Institute for Cell Engineering. The therapeutic promise of human stem cells is derived from their ability to develop into any kind of cell and, in theory, regenerate injured or diseased tissues ranging from the insulin-making islet cells of the pancreas that are lost in type 1 diabetes to the dopamine-producing brain cells that die off in Parkinson’s disease.
Ten years ago, Shinya Yamanaka’s research group in Japan raised hopes further when it developed a technique for “resetting” mature cells, such as skin cells, to become so-called induced pluripotent stem cells. That gave researchers an alternative to embryonic stem cells that could allow the creation of therapeutic stem cells that matched the genetic makeup of each patient, greatly reducing the chances of cell rejection after they were infused or transplanted. But while induced pluripotent stem cells have enabled great strides forward in research, Walczak says they are not yet approved for any treatment, and barriers to success remain.
In a bid to address once such barrier – how to get the cells exactly where needed and no place else – Walczak and his colleague Miroslaw Janowski, M.D., Ph.D., assistant professor of radiology, sought a way around strategies that require physicians to puncture patients’ skulls or inject them intravenously. The former, Walczak says, is not only unpleasant, but also only allows delivery of stem cells to one limited place in the brain. In contrast, injecting cells intravenously scatters the cells throughout the body, with few likely to land where they’re most needed, says Walczak.
“Our idea was to do something in between,” says Janowski, using intra-arterial injection, which involves threading a catheter, or hollow tube, into a blood vessel, usually in a leg, and guiding it to a vessel in a hard-to-reach spot like the brain. The technique currently is used mainly to repair large vessels in the brain, says Janowski, but the research team hoped it might also be used to get stem cells to the exact place where they were needed. To do that, they would need a way of monitoring the catheter placement and movement of implanted cells in real time.
Walczak and Janowski teamed with colleagues including Monica Pearl, M.D., an associate professor of radiology practicing in the Division of Interventional Neuroradiology, who specializes in intra-arterial procedures. Usually the procedure is performed using an X-ray image as a guide, but that approach ruled out watching injected stem cells’ movements and making adjustments in real time.
In their experiments, after placing the catheter under X-ray guidance, they transferred anesthetized dog and pig subjects to an MRI machine, where images were taken every few seconds throughout the procedure. Once the catheter was in the brain, Pearl pre-injected small amounts of a harmless contrast agent that included iron oxide and could be detected on the MRI. “By using MRI to see in real time where the contrast agent went, we could predict where injected stem cells would go and make adjustments to the catheter placement, if needed,” says Janowski. Adds Jeff Bulte, Ph.D., a professor of radiology who participated in the study, “It’s like having GPS guidance in your car to help you stay on the right route, instead of only finding out you’re lost when you arrive at the wrong place.”
The team then injected both small stem cells (glial progenitor cells from the brain) and large mesenchymal stem cells from bone marrow into the animals under MRI, and found that in both cases, the pre-injected contrast agent and MRI allowed them to accurately predict where the cells would end up. They could also tell whether clumps of cells were forming in arteries and, if so, possibly intervene to avoid letting the clumps grow large enough to cut off blood flow and pose a danger. “If further research confirms our progress, we think this procedure could be a big step forward in precision medicine, allowing doctors to deliver stem cells or medications exactly where they’re needed for each patient,” says Walczak. The research team is planning to test the procedure in animals as a treatment for stroke and cancer, delivering both medications and stem cells while the catheter is in place.
Other authors on the paper are Joanna Wojtkiewicz, Aleksandra Habich, Piotr Holak, Zbigniew Adamiak and Wojciech Maksymowicz of the University of Warmia and Mazury in Poland; Adam Nowakowski and Barbara Lukomska of the Mossakowski Medical Research Center in Poland; Jiadi Xu of the Kennedy Krieger Institute; and Moussa Chehade and Philippe Gailloud of the Johns Hopkins University.
The study was funded by the National Institute of Neurological Disorders and Stroke (grant numbers NS076573, NS045062, NS081544), the Maryland Stem Cell Research Fund, the Department of Defense (grant number PT120368), the Polish National Science Centre (grant number NCN 2012/07/B/NZ4/01427), the National Centre for Research and Development, and a Mobility Plus Fellowship from the Polish Ministry of Science and Higher Education.
<blockquote>"One would hope that this kind of paper would be retracted by the journal..."</blockquote>
Honestly, one would hope that the journal editors themselves would catch simple issues like this before they even sent the paper for review, particularly in cases in which the authors don't have the integrity to not submit such pablum in the first place.
[1608.00462] Are Safer Looking Neighborhoods More Lively? A Multimodal Investigation into Urban Life
Authors: Marco De Nadai, Radu L. Vieriu, Gloria Zen, Stefan Dragicevic, Nikhil Naik, Michele Caraviello, Cesar A. Hidalgo, Nicu Sebe, Bruno Lepri
To appear in the Proceedings of ACM Multimedia Conference (MM), 2016. October 15 - 19, 2016, Amsterdam, Netherlands
Policy makers, urban planners, architects, sociologists, and economists are interested in creating urban areas that are both lively and safe. But are the safety and liveliness of neighborhoods independent characteristics? Or are they just two sides of the same coin? In a world where people avoid unsafe looking places, neighborhoods that look unsafe will be less lively, and will fail to harness the natural surveillance of human activity. But in a world where the preference for safe looking neighborhoods is small, the connection between the perception of safety and liveliness will be either weak or nonexistent. In this paper we explore the connection between the levels of activity and the perception of safety of neighborhoods in two major Italian cities by combining mobile phone data (as a proxy for activity or liveliness) with scores of perceived safety estimated using a Convolutional Neural Network trained on a dataset of Google Street View images scored using a crowdsourced visual perception survey. We find that: (i) safer looking neighborhoods are more active than what is expected from their population density, employee density, and distance to the city centre; and (ii) that the correlation between appearance of safety and activity is positive, strong, and significant, for females and people over 50, but negative for people under 30, suggesting that the behavioral impact of perception depends on the demographic of the population. Finally, we use occlusion techniques to identify the urban features that contribute to the appearance of safety, finding that greenery and street facing windows contribute to a positive appearance of safety (in agreement with Oscar Newman's defensible space theory). These results suggest that urban appearance modulates levels of human activity and, consequently, a neighborhood's rate of natural surveillance
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@cesifoti This paper on history and complexity/network theory made me think of some of your work: http:/
#IndieWeb Raison d'etre #55: Freedom of the press trumps atrocious comment moderation
2 min read
Last week I wrote up "" after reading “” from Science | AAAS which made some heavy rounds in social media, particularly in academic spheres. Originally I began typing my thoughts/comments into the Disqus box on their website. After getting to the third graph, I began thinking, I should be writing this on my own website as a standalone comment/piece of content and just POSSE it over to their Disqus box.
Despite the fact that the editors/moderators of one of the most venerable science journals of our day will allow internet trolls like CPO_C_Ryback and CPO_C_Rybacks_Mother to go thirty rounds on nearly every comment on their featured piece for the week, my slightly more tempered comment is still sitting in their moderation queue untouched.
Fortunately I had the foresight to have self-published it before hand, or the not-insignificant time I spent thinking and writing about the topic at hand would have been gone the moment I pressed send. It's one thing to get lost in the shuffle of hundreds of comments amidst trolls, it's another thing altogether to be moderated out of existence. The IndieWeb movement has prevented me from feeling like I did two decades ago after writing a term paper for hours only to lose it after discovering that I hadn't hit control-s to save what I'd written. The additional benefit was that I was able to post those same thoughts on multiple other networks effortlessly while still being able to own what I'd originally written.
The greatest irony of the whole affair is that in conjunction with the particular article I was commenting on, Marcia McNutt, Editor-in-Chief Science Journals, about the high costs and attention to detail and quality that journals try to maintain in their digital presence. Apparently this massive expense and terrific effort doesn't go as far as preventing internet trolls like those mentioned from running roughshod over their own site (which is "moderated" by the way) while keeping out commentary that may add to the discussion and community that they're apparently not attempting to foster.
#sciencecommunication #publishing #indieweb #academicsamizdat
@fermatslibrary It seems easier for me to annotate @preskill's paper on Hypothes.is and Genius.com than it does on your platform. The load times for the left side bar seem atrocious. Potentially a fantastic product. Love the particular subject matter you're highlighting.
I'm a sucker for notebook journalism | Pocket Paper Notebook Showdown: Moleskine vs. Field Notes http:/
How to review a paper http:/
I admit that did expect something more entertaining (an Easter egg perhaps?) from Google when I searched for the phrase "what will happen if I squeeze a paper cup full of hot coffee?"
The advantage of simple paper abstracts http:/
My reply to ‘Novel, amazing, innovative’: positive words on the rise in science papers | Nature News & Comment
http:/
I can readily posit a potential and very strong motivation for the uptick in the appearance of these words, and particularly for the word "novel", which the paper and this article fail to see.
Beginning in the early 90's, and certainly starting before that time, there has been an intensified interest for both research institutions and researchers writing papers for them to monetize their research outside the halls of the academy. (Particularly with decreased funding for faculty and intensified competition for research dollars - many research faculty either self-fund their salaries or rely heavily on 3rd party income.) Toward this end, individual researchers began more aggressively pursuing patents for their research work and at the institutional level, colleges and universities began very actively pursuing technology transfer to the point of opening up full offices and hiring large numbers of staff to better leverage the return of creating patents and pursuing sales and licensing deals for the resulting research work. The US Patent Office, in making a determination of whether or not to grant patents, (and even moreso when the underlying documents are published scientific research articles) uses words like "novel" and "innovative" as an indicator of their worthiness. Without a patent, it's incredibly difficult to protect the intellectual property contained within a published and public work. Other words like "amazing" which are also cited in the paper are geared (in a business sales sense) more toward potential corporate financial investors who may consider purchasing or licensing the resulting work of a research paper. What corporate bean counter wants to invest in a dull-sounding research paper title which is quite likely one of the only parts of the document they're likely to comprehend? Yet throw in some "excitement words" and you may have a sale!
When one looks at employment contracts of the professoriate (post-docs, graduate students, and the like), which presumably comprises the majority of those publishing papers with these words, one will see that professors prior to the 90's have contracts that don't mention intellectual property rights resulting from their efforts, or which grant them the lion's share. Current contracts after that period will almost necessarily keep either all or most of these types of revenue streams in the institution's pockets rather than the researchers themselves. I'd be willing to bet that this tide began turning in the mid-1970s and has certainly been overwhelming since the mid-90s.
It is these severe economic taskmasters which are almost assuredly the cause of the rise of these buzzwords in research papers, and most particularly in their titles. One need only ask themselves, which university wants to be the next proverbial "Stanford" to not have a piece of revenue from the intellectual property of a proverbial "Page rank" algorithm? Or in biomedical research, to not take a hefty cut out of a drug which could potentially cure cancer or HIV/AIDS? Take a gander at what something as simple as a HELA cell, which was taken and cultured without any notice to Henrietta Lacks, has become from an industrial perspective. If they can avoid it, academia certainly won't let multi-million (or billion) dollar enterprises spring up (again) without them receiving a piece of the pie.
Naturally, there are other factors compounding the issues at hand, particularly when one looks at negative research findings, which are sadly rarely ever published, particularly in an era of big data when what we know isn't true will surely help assist in defining the boundaries of what we do know and what could potentially be determined at that boundary. (Much the way that white space in photographs or in printed pages helps to define an image as much if not more so than the darker portions of the image.) Negative words are likely more difficult to get published as it may reflect poorly on researchers who are reliant on continued future funding and may see their sources disappear when they're not producing groundbreaking work. My hypothesis, however, is that it's more likely a direct economic impact based on technology transfer than it is the increased competitive landscape in academic research.