STARSTEM Publications

STARSTEM Journal Articles

2020

  • W. Hotham, and F.M.D. Henson “The use of large animals to facilitate the process of MSC going from laboratory to patient-‘bench to bedside’.” Cell Biol Toxicol 2020 DOI: 10.1007/s10565-020-09521-9
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Large animal models have been widely used to facilitate the translation of mesenchymal stem cells (MSC) from the laboratory to patient. MSC, with their multi-potent capacity, have been proposed to have therapeutic benefits in a number of pathological conditions. Laboratory studies allow the investigation of cellular and molecular interactions, while small animal models allow initial ‘proof of concept’ experiments. Large animals (dogs, pigs, sheep, goats and horses) are more similar physiologically and structurally to man. These models have allowed clinically relevant assessments of safety, efficacy and dosing of different MSC sources prior to clinical trials. In this review, we recapitulate the use of large animal models to facilitate the use of MSC to treat myocardial infarction-an example of one large animal model being considered the ‘gold standard’ for research and osteoarthritis-an example of the complexities of using different large animal models in a multifactorial disease. These examples show how large animals can provide a research platform that can be used to evaluate the value of cell-based therapies and facilitate the process of ‘bench to bedside’.

2019

  • Sergey Alexandrov, Paul M. McNamara, Nandan Das, Yi Zhou, Gillian Lynch, Josh Hogan, and Martin Leahy. “Spatial frequency domain correlation mapping optical coherence tomography for nanoscale structural characterization” Applied Physics Letters 115(2) 2019 DOI: https://doi.org/10.1063/1.5110459
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Most of the fundamental pathological processes in living tissues exhibit changes at the nanoscale. Noninvasive, label-free detection of structural changes in biological samples pose a significant challenge to both researchers and healthcare professionals. It is highly desirable to be able to resolve these structural changes, during physiological processes, both spatially and temporally. Modern nanoscopy largely requires labeling, is limited to superficial 2D imaging, and is generally not suitable for in vivo applications. Furthermore, it is becoming increasingly evident that 2D biology often does not translate into the real 3D situation. Here, we present a method, spatial frequency domain correlation mapping optical coherence tomography (sf-cmOCT), for detection of depth resolved nanoscale structural changes noninvasively. Our approach is based on detection and correlation of the depth resolved spectra of axial spatial frequencies of the object which are extremely sensitive to structural alterations. The presented work describes the principles of this approach and demonstrates its feasibility by monitoring internal structural changes within objects, including human skin in vivo. Structural changes can be visualized at each point in the sample in space from a single image or over time using two or more images. These experimental results demonstrate possibilities for the study of nanoscale structural changes, without the need for biomarkers or labels. Thus, sf-cmOCT offers exciting and far-reaching opportunities for early disease diagnosis and treatment response monitoring, as well as a myriad of applications for researchers.

What are you aiming to find out?

Development of the new technologies for visualization of the sub-micron structure with nanoscale sensitivity to structural changes.

Why does this research need to be done?

For both the fundamental study of biological processes and early diagnosis of pathological processes, information about nanoscale tissue structure is crucial. Furthermore, it is becoming increasingly evident that 2D biology often does not translate into the real 3D situation. The research is motivated by current needs of optical science and technology for biomedical and other applications and is devoted to an important fundamental problem: investigation of new possibilities to detect the structural changes within 3D objects without labels by providing nanoscale sensitivity to structural alterations. One of the most appreciated and fast developed techniques for 3D biomedical imaging is optical coherence tomography (OCT), but resolution and sensitivity to structural alterations is typically limited to microscale. Proposed approach permits to dramatically improve sensitivity to structural changes, up to nanoscale, using just single frame.

Describe the methods chosen.

Label free non-contact optical imaging technologies have been developed. The ability to detect nano-scale structural changes has been demonstrated using different phantoms and human skin in vivo. Healthy volunteer was involved in this study.

What is the intended impact and how can others use the research?

According to the STARSTEM project these techniques will be used to detect changes in cell morphologies and extracellular vesicles at the nanometer scale; to investigate the potential of imaging of extracellular vesicle-mediated disease responses; for nanosensitive detection of tissue responses to disease.

What are the next steps?

  • Experiments to perform nanosensitive detection of tissue responses to disease.
  • Further development of these optical technologies.

Related research.

  1. Alexandrov, P. M. McNamara, N. Das, Y. Zhou, G. Lynch, J. Hogan, and M. Leahy “Spatial frequency domain correlation mapping optical coherence tomography for nanoscale structural characterization”. Appl. Phys. Lett. 2019, v.115, N12, 121105. https://doi.org/10.1063/1.5110459.
  2. Alexandrov, N. Das, J. McGrath, P. Owens, C. J. R. Sheppard, F. Boccafoschi, C. Giannini, T. Sibillano, H. Subhash, and M. Leahy. “Label free ultra-sensitive imaging with sub-diffraction spatial resolution”. 21st International Conference on Transparent Optical Networks ICTON, July 9-13, 2019 Angers, France, Invited, IEEE-Xplore Proceedings 2019 Fr.A6.3, pp.1-4. https://ieeexplore.ieee.org/xpl/conhome/1000766/all-proceedings

STARSTEM Conference Publications

2019

  • Sergey Alexandrov, Nandan Das, James McGrath, Peter Owens, Colin J. R. Sheppard, Francesca Boccafoschi, Cinzia Giannini, Teresa Sibillano, Hrebesh Subhash, and Martin Leahy. “Label free ultra-sensitive imaging with sub-diffraction spatial resolution” Paper presented at the 21st International Conference on Transparent Optical Networks, ICTON’2019, Angers, France, 09-13 July.  DOI: https://dx.doi.org/10.1109/ICTON.2019.8840220
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In this paper, we show a new way to break the resolution limit and dramatically improve sensitivity to structural changes. To realize it we developed a novel label free contrast mechanism, based on the spectral encoding of spatial frequency (SESF) approach. The super-resolution SESF (srSESF) microscopy is based on reconstruction of the axial spatial frequency (period) profiles for each image point and comparison of these profiles to form super-resolution image. As a result, the information content of images is dramatically improved in comparison with conventional microscopy. Numerical simulation and experiments demonstrate significant improvement in sensitivity and resolution.

  • Sergey A. Alexandrov, James McGrath, Colin Sheppard, Francesca Boccafoschi, Cinzia Giannini, Teresa Sibillano, Hrebesh Subhash, Josh Hogan, and Martin Leahy. “Ultra-sensitive label free imaging below the resolution limit” Paper presented at the SPIE BiOS 2019 meeting, San Francisco, California, USA, 4 March 2019.  DOI: https://doi.org/10.1117/12.2502479
    Download the pdf here.

Almost all known nanoscopy methods rely upon the contrast created by fluorescent labels attached to the object of interest. This causes limitations on their applicability to in vivo imaging. A new label-free spectral encoding of spatial frequency (SESF) approach to nanoscale probing of three-dimensional structures has been developed. It has been demonstrated that spatial frequencies, encoded with optical wavelengths, can be passed though the optical system independent of the resolution of the imaging system. As a result information about small size structures can be detected even using a low resolution imaging system. Different versions of the SESF imaging have been published [1-7], including a novel contrast mechanism for high resolution imaging [1], real time nano-sensitive imaging [2], reconstruction the axial (along depth) spatial frequency profiles for each point with nano-sensitivity to structural changes [3], and the adaptation of the SESF approach to depth resolving imaging [4,5]. Recently the SESF approach has been applied to break the diffraction limit and dramatically improve resolution [6,7]. Here we present further development of the SESF approach including correlation mapping SESF imaging. Both results of numerical simulation and preliminary experimental results, including biological objects, will be presented. [1] Alexandrov, et.al., Opt. Lett. 36 3323 (2011). [2] Alexandrov, et.al., Opt. Express 20 (8) 9203 (2012). [3] Alexandrov, et.al., Appl. Phys. Let., 101 033702 (2012). [4] Uttam, et.al., Opt. Express, 21, 7488 (2013). [5] Alexandrov, et.al., Nanoscale, 6, 3545 (2014). [6] Alexandrov, et.al., Sci. Rep., 5, doi: 10.1038/srep13274 (2015). [7] Alexandrov, et.al., J. Biophotonics, https://doi.org/10.1002/jbio.201700385 (2018).