New technologies in stem cell biology and a call to reach back in time

Author: David Kent, 03/22/11

I recently attended a special conference on Stem Cells, Development, and Cancer run by the American Association for Cancer Research (AACR) where Connie Eaves from the British Columbia Cancer Agency chaired a session entitled “Emerging Technologies” and said something that rang very true to me. She challenged the audience to read the papers from their field that were written many years ago and look for the ideas and hypotheses being tested and ask themselves how similar they are to those being pursued today – they simply lacked the tools to address them. In short, she made a very strong case for the importance of novel technologies and for biologists to be particularly tuned in to new developments and how they can impact their research. Anecdotally, I was once asked by Connie in my PhD to read a particular paper on the heterogeneity of blood cell progeny that, to my surprise, spelled out many of the theories and questions I was pursuing in my own studies. From a theoretical perspective, the testing framework had all been outlined in this paper and practically carried out in a more mature cell compartment. The really humbling part was that this particular report was published in 1982… when I was one. What has changed, of course, is that emerging technologies (in this case, the ability to isolate highly enriched fractions of stem cells and cell culture conditions to keep them alive and in the stem cell state) have made it possible to find answers to these questions, which has moved our understanding of stem cells forward. However, it is interesting to note that the researchers from 1982 would have happily done the same experiments if they’d only had the tools at their disposal.

Of particular interest at the AACR conference were two new methods for helping to understand stem cells: microfluidics and mass spectrometry cytometry. First, microfluidics allows cell culture experiments and molecular biology experiments to be done in remarkably small volumes of liquid and has a particular utility in stem cell biology where experiments are often limited by expensive cytokines and more recently have required study of large numbers of single stem cells to assess the heterogeneity in growth, differentiation, divisional kinetics, and survival. Carl Hansen and Darek Sikorski from the University of British Columbia presented work in the embryonic and hematopoietic stem cell systems, replicating published data from batch cultures and producing new comprehensive data about cytokine regulation in HSCs that would be unmanageable to acquire in current 96 well plate systems. Second, mass spectrometry-based cytometry is a new technology that allows enormous multiplexing not possible in current flow cytometry methods. Instead of using antibodies conjugated to fluorochromes, mass spectrometry cytometry conjugates antibodies to metals that are subsequently separated by mass spectrometry. Erin Simonds from Garry Nolan’s group at Stanford University presented that mass spectrometry cytometry currently allows 34 different antibodies to be detected simultaneously with no need for compensation and has the possibility to go up to 100 colours. This technology could revolutionize the characterization of stem cells, especially as more tools become available for intracellular staining, phosphorylation status, etc.

In the end, these developments should inspire throngs of young researchers to invest time in developing new tools to make doable those things that were previously not possible. Just because it isn’t online, doesn’t mean that it isn’t valuable and we should all take a few moments to scour the literature from our field and related fields to dig up the “oldies” to understand and build on the thinking that has already been done.

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David Kent

David Kent

Principal Investigator at University of Cambridge
Dr. David Kent is a Principal Investigator at the University of Cambridge in the Cambridge Stem Cell Institute (http://www.stemcells.cam.ac.uk/researchers/principal-investigators/dr-david-kent). His laboratory's research focuses on fate choice in single blood stem cells and how changes in their regulation lead to cancers. David is currently the Stem Cell Institute’s Public Engagement Champion and has a long history of public engagement and outreach including the creation of The Black Hole in 2009. He has been writing for Signals since 2010.
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One Response

  1. Biospherix says:

    Amazing what you can learn when you truly scour the archives on a given topic. More attention to the past both success and failures if woven into the fabric of modern research could result in rapid progress in certain niches. It seems amazing with the advances in machine learning and text mining we haven’t uncovered other long forgotten about substances or combinations. Take oxygen for example, amazing that some understand what physiologic oxygen is but they are indeed in the minority. The importance of Oxygen was uncovered several decades ago. Only now are the discoveries beginning to steamroll in oxygen’s important role in cell biology.

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