Theranostics 2018; 8(10):2657-2671. doi:10.7150/thno.23206

Research Paper

Caveolae-mediated mesenchymal stem cell labelling by PSS-coated PLGA PFOB nano-contrast agent for MRI

Hieu Vu Quang1*, Chi-Chih Chang1*✉, Ping Song1, Ellen-Margrethe Hauge2,3, Jørgen Kjems1

1. Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Denmark, Center for Cellular Signal Patterns (CellPat), Aarhus University, Denmark
2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
3. Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
* equal contribution

Abstract

Rationale: Non-invasive tracking of transplanted cells is critical in evaluating delivery, migration and prognosis of cell therapies.

Methods: We formulated a nano-contrast agent consisting of a perfluorooctylbromide (PFOB) core within a shell of poly (lactic-co-glycolic acid) (PLGA) followed by a coat of polystyrene sulfonate (PSS) for 19F MRI. The nano-contrast agent (PSS-NP) was characterised by DLS and the uptake efficiency of the nano-contrast agent (PSS-NP) was tested using flow cytometry, in vitro MRI and confocal microscopy. In vitro and in vivo assays of labelled cells were tested for their ability to provide an MRI signal while retaining their osteoblastic differentiation capabilities.

Results: PSS-NPs were internalised via caveolae-mediated endocytosis in mesenchymal stromal/stem cells without affecting cell proliferation and differentiation in osteoblasts, both in vitro and in vivo. Furthermore, labelled cells were monitored by 19F MRI for up to 2 months after transplantation in mice. In particular, PSS-NP-labelled cells can be used to monitor the enhanced immune rejection of grafted human cells in normal BALB/c mice compared to immune-compromised NOD/SCID mice. One week after transplantation, 40% of the 19F MRI signal was lost in normal mice, whereas only 10% was lost in immune-compromised mice.

Conclusion: Overall, these results show that PSS-NPs can label MSCs effectively, and be employed in vivo as a novel nano-contrast agent for non-invasive cell tracking using clinically relevant 19F MRI techniques.

Keywords: stem cell therapy, MRI, contrast agent, caveolae-mediated endocytosis, mesenchymal stem cells, nanoparticles

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How to cite this article:
Quang HV, Chang CC, Song P, Hauge EM, Kjems J. Caveolae-mediated mesenchymal stem cell labelling by PSS-coated PLGA PFOB nano-contrast agent for MRI. Theranostics 2018; 8(10):2657-2671. doi:10.7150/thno.23206. Available from http://www.thno.org/v08p2657.htm