Icon for: Heather Huntsman

HEATHER HUNTSMAN

University of Illinois at Urbana-Champaign
Years in Grad School: 3

Judges’ Queries and Presenter’s Replies

  • May 20, 2013 | 03:06 p.m.

    Hello heather. What is the physiological equivalent of the mechanical strain preconditioning in your protocol? Would such strain correspond to, say, physical exercise in human? Can you clarify what the values in Figure 1A correspond to?
    JB

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:00 p.m.

    Yes exercise, and more specifically eccentric, or lengthening, contraction, is the physiologic equivalent. Our lab has recently established a role for mMSCs in vessel and muscle growth within young skeletal muscle (Leuders Am J Physiol 2010, Valero PLoS One 2012, Huntsman Am J Physiol 2013). A key signal for this event seems to be mechanical strain, which in our in vivo model is downhill treadmill running exercise.

    The values in Figure 1A are the mechanical strain parameters. mMSCs were given 24 hours to attach to a laminin coated bioflex membrane. Following this attachment period, the cells were strained in both the x and y direction at a cell deformation percentage of 10. This was done cyclicly at a rate of 1 stretch per second, for 5 hours.

  • May 21, 2013 | 10:45 a.m.

    Hi! What paracrine factors influence this study? Is it concentration dependent?

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:00 p.m.

    While our hypothesis is that the strength and novelty of this therapy lies in the release of several factors in a coordinated and responsive manner, we are particularly interested in insulin like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) for their potential effects on muscle, vessel and neural tissue, respectively (Marini Eur J Trans Myology 2010, Gopinath Aging Cell 2010, Parvaresh Exp Physiol 2010). I am unable to answer the second part of your question at this point, but one of my specific aims in this study is to assess the release kinetics of each of these specific factors, and determine whether there is a threshold for adaptive responses.

  • May 21, 2013 | 11:24 a.m.

    Is the response to mechanical stress specific to mMSC? How do other cells respond with respect to paracrine signalling?

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:01 p.m.

    Increased paracrine factor release in response to mechanical stress is not a phenomenon observed solely in mMSCs. There are several other cell types that respond in a similar manner (e.g. other muscle derived stem cell populations (Cassino Tissue Eng Part A 2012), mesenchymal stem cells from other tissues such as bone marrow derived MSCs and adipose derived MSCs (Ranganath Cell 2012), several cardiac cell populations (Ruwhof Arch Physiol Biochem 2001, van Wamel Mol Cell Biochem 2001), and myocytes (Pederson J Exp Bio 2011)). What varies is the specific factors that are released, and the type of mechanical stimuli that drive this response.

    We are still in the process of fully understanding the adaptations driven by paracrine mediated mechanisms. Based the data we have collected and the current literature we think that the factors being released are ameliorating the chronic low grade inflammatory environment, increasing smooth muscle and endothelial cell proliferation leading to vessel growth, and increasing the survival and stability of the neuromuscular junctions (Payne J Physiol 2006, Ranganath Cell 2012, da Silva Meirelles Cytokine Growth Factor Rev 2009).

  • May 21, 2013 | 04:07 p.m.

    Hi Heather: Interesting work! By denervation are you speaking of the loss of entire motor units, or nerves within those motor units? The reason I ask is that your metric is based on synaptophysin, a synaptic vesicle marker – could it be that neurotransmitter release is the factor being affected?

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:01 p.m.

    Based on the literature, age-related denervation is a result of both ?-motorneuron apoptosis and the loss of myelinated nerve fibers (Doherty J Appl Physiol 2003, Larsson Prog Neurobiol 1995). I have been unable to find studies that have specifically evaluated neurotransmitter release in aged skeletal muscle, which doesn’t mean that it isn’t affected, I just can’t directly address the question. You bring up a very interesting point though, and it is something that I will definitely keep in mind as I move forward with this project. My decision to use synaptophysin as a pre-synaptic marker was based on the work by Storkebaum et al. (Nature 2005), where they evaluated the effect of VEGF treatment on the innervation of skeletal muscle using a rat model of ALS.

  • Icon for: Zhaomin Yang

    Zhaomin Yang

    Judge
    May 21, 2013 | 08:06 p.m.

    Very intriguing work. What was the number of mMSCs transplanted into each animal, how was the number determined and how does it compare with the endogenous population?

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:02 p.m.

    There is a wide range of stem cell transplantation protocols in the literature (e.g. 30,000 to 1,000,000 cells/transplantation), but in an attempt to transplant unpassaged, freshly isolated mMSCs with the greatest potential we decided to transplant 40,000 cells per gastrocnemius/soleus complex. This number was also based on a very similar study where 30,000 muscle derived stem cells (MDSCs) were transplanted into mouse hearts, post infarct, where vessel growth and immunomodulating affects were observed (Cassino Tissue Eng Part A 2012).

    We are currently in the process of quantitatively assessing the number mMSCs in aged skeletal muscle through flow cytometry. That said, based on our preliminary qualitative immunohistochemistry data this cell population is greatly decreased in aged tissue. So, as for how this number compares to the endogenous population, it is several fold higher.

  • Further posting is closed as the competition has ended.

Presentation Discussion
  • Icon for: Martha Gillette

    Martha Gillette

    Faculty
    May 21, 2013 | 05:01 p.m.

    Interesting, informative, and forward-looking. Great job, Heather!!!

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:06 p.m.

    Thanks, Dr. Gillette. I’m very excited about this project. Thanks for taking the time to watch my video and check out my poster. I appreciate it.

  • Icon for: Carlos Dostal

    Carlos Dostal

    Trainee
    May 21, 2013 | 08:49 p.m.

    I also enjoyed your video Heather. The aerospace engineer in me became very excited connecting your work to space medical research and zero-gravity induced musculoskeletal loss. Beautiful micrographs on your poster too!

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:07 p.m.

    Thanks Carlos. There is definitely overlap there. And thanks, imaging is one of my favorite parts of my job. :)

  • Icon for: Laura Miller

    Laura Miller

    Coordinator
    May 22, 2013 | 12:00 a.m.

    Great job making your work understandable to a general audience!

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:08 p.m.

    Thanks Laura. I appreciate all you do to support us, and I wouldn’t be doing what I do without people like you.

  • Icon for: Marni Boppart

    Marni Boppart

    Faculty
    May 22, 2013 | 09:35 a.m.

    Very professional. Nice job, Heather!

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:09 p.m.

    Thanks Marni. I was honored to have the opportunity to represent our lab on a national stage.

  • Icon for: Erich Lidstone

    Erich Lidstone

    Trainee
    May 22, 2013 | 11:59 a.m.

    The visuals are great, and your explanation is super accessible, especially with work of this complexity. Great presentation; I was going to ask about some more details of the procedures you use (tough to address in such a short time!), but I see there is plenty of that on the poster. Strong work, and good luck!

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:10 p.m.

    Thanks Erich. I appreciate it. Thanks for taking the time to watch my video and check out my poster. I’m incredibly excited about this project.

  • Icon for: Eric Jakobsson

    Eric Jakobsson

    Faculty
    May 22, 2013 | 07:15 p.m.

    Very interesting project. One question I have: is injecting the stem cells necessary, or even the best thing to do? Would it be possible to apply the tension to the stem cells in a flow chamber and inject the fluid that includes the material that the stem cells secrete under tension into the muscle. I make the suggestion because the results you see are suggestive but marginal, at least so far. Perhaps this alternative technique could provide more of an effect—or of course, maybe none, who knows? But I was following up on the leadin to the project, which stated that the effects of the stem cells are due to what they secrete under tension.

  • Icon for: Heather Huntsman

    Heather Huntsman

    Presenter
    May 22, 2013 | 07:27 p.m.

    Thank you for your interest in my work. While injecting the conditioned media may have some positive effects, they would be transient. The strength of injecting the cells is that they can continue to respond to the microevironment, producing and releasing factors as necessary. It is true that the results are marginal, but we specifically chose to look at an early time point (i.e. 7 days) in order to better understand the adaptive process. The follow up to this study is to look at later time points, as well as to optimize the number of transplantations in order to maximize the revitalization of muscle mass and function.

  • May 23, 2013 | 11:47 a.m.

    Great job, Heather! You always present your work in a manner that is succinct and accessible, yet still technical and professional.

  • Further posting is closed as the competition has ended.