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Siloxane Nanoprobes for Labeling and Dual Modality Functional Imaging of Neural Stem Cells

  • Nondestructive Characterization of Biomaterials for Tissue Engineering and Drug Delivery
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Abstract

Cell therapy represents a promising therapeutic for a myriad of medical conditions, including cancer, traumatic brain injury, and cardiovascular disease among others. A thorough understanding of the efficacy and cellular dynamics of these therapies necessitates the ability to non-invasively track cells in vivo. Magnetic resonance imaging (MRI) provides a platform to track cells as a non-invasive modality with superior resolution and soft tissue contrast. We recently reported a new nanoprobe platform for cell labeling and imaging using fluorophore doped siloxane core nanoemulsions as dual modality (1H MRI/Fluorescence), dual-functional (oximetry/detection) nanoprobes. Here, we successfully demonstrate the labeling, dual-modality imaging, and oximetry of neural progenitor/stem cells (NPSCs) in vitro using this platform. Labeling at a concentration of 10 μL/104 cells with a 40%v/v polydimethylsiloxane core nanoemulsion, doped with rhodamine, had minimal effect on viability, no effect on migration, proliferation and differentiation of NPSCs and allowed for unambiguous visualization of labeled NPSCs by 1H MR and fluorescence and local pO2 reporting by labeled NPSCs. This new approach for cell labeling with a positive contrast 1H MR probe has the potential to improve mechanistic knowledge of current therapies, and guide the design of future cell therapies due to its clinical translatability.

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Acknowledgments

The authors would like to acknowledge David Menn, Arizona State University, and Qingwei Liu, Barrow Neurological Institute, for technical assistance. These studies were supported by a Rising Stars in Engineering seed grant from College of Engineering, ASU (VDK and SES) and NIH 1DP2HD084067 (SES).

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Authors and Affiliations

  1. School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA

    Caroline P. Addington, Alex Cusick, Rohini Vidya Shankar, Shubhangi Agarwal, Sarah E. Stabenfeldt & Vikram D. Kodibagkar

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  1. Caroline P. Addington
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  3. Rohini Vidya Shankar
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Correspondence to Sarah E. Stabenfeldt or Vikram D. Kodibagkar.

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Associate Editor Agata Exner oversaw the review of this article.

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10439_2015_1514_MOESM1_ESM.tif

Flow cytometry scatter and gating of labeled NSPCs stained with calcein AM. Based on gating, indicated by black outline, NPSCs labeled at 1 μL/104 cells (B) did not exhibit an increase in the dead (gated) population compared to unlabeled NPSCs (A). At 5, 10 and 50 μL/104 cells labeling concentration, the dead population increased to 11.7%, 19.9% and 35.4% respectively (C-E). (TIFF 20116 kb)

10439_2015_1514_MOESM2_ESM.tif

NPSC radial migration on poly-L-lysine (PLL) and laminin out to 6 days. Minimal radial migration is observed on PLL at days 0, 3 and 6 for both unlabeled (A-C) and labeled (D-F) NPSCs. However, increased radial migration is observed on laminin at days 3 and 6 compared to day 0 and to PLL controls for both unlabeled (G-I) and labeled (J-L) NPSCs. Positive rhodamine B staining is indicative of labeling (D-F, J-L). Scale bar is 150 μm. (TIFF 63681 kb)

10439_2015_1514_MOESM3_ESM.tif

R1 versus pO2 calibration curves for PDMS nanoemulsion. R1 values of tubes with nanoemulsions equilibrated at 0%, 10%, and 21% atm oxygen (0, 76 and 160 torr respectively) and sealed show the expected linear dependence on pO2. Fitting yielded following calibration constants: intercept A’ = 0.235 ± 0.006 s-1 and slope B’ = (1.30 ± 0.08)X10-3 (s torr)-1, (R2 >0.99) at 23 ºC and A’ = 0.207 ± 0.001 s-1 and B’ = 1.25 ± 0.01)X10-3 (s torr)-1, (R2 >0.99) at 33.5 ºC. (TIFF 30081 kb)

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Addington, C.P., Cusick, A., Shankar, R.V. et al. Siloxane Nanoprobes for Labeling and Dual Modality Functional Imaging of Neural Stem Cells. Ann Biomed Eng 44, 816–827 (2016). https://doi.org/10.1007/s10439-015-1514-1

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