Abstract

Oligodendrocyte precursor cells (OPCs) have shown high promise as a transplant population to promote regeneration in the central nervous system, specifically, for the production of myelin – the protective sheath around nerve fibers. While clinical trials for these cells have commenced in some areas, there are currently key barriers to the translation of neural cell therapies. These include the ability to (a) image transplant populations in vivo; (b) genetically engineer transplant cells to augment their repair potential; and (c) safely target cells to sites of pathology. Here, we review the evidence that magnetic nanoparticles (MNPs) are a ‘multifunctional nanoplatform’ that can aid in safely addressing these translational challenges in neural cell/OPC therapy: by facilitating real-time and post-mortem assessment of transplant cell biodistribution, and biomolecule delivery to transplant cells, as well as non-invasive ‘magnetic cell targeting’ to injury sites by application of high gradient fields. We identify key issues relating to the standardization and reporting of physicochemical and biological data in the field; we consider that it will be essential to systematically address these issues in order to fully evaluate the utility of the MNP platform for neural cell transplantation, and to develop efficacious neurocompatible particles for translational applications.Electronic supplementary materialThe online version of this article (doi:10.1186/2052-8426-2-23) contains supplementary material, which is available to authorized users.

Highlights

  • OPC transplantation therapies for regenerative neurology Oligodendrocyte precursor cells (OPCs) are proliferative, stem-like cells of the central nervous system (CNS) that have emerged as a key transplant population to promote repair of myelin [1]

  • We have shown that Magnetic nanoparticle (MNP) can deliver both reporter and therapeutic genes to OPCs, a process significantly enhanced by the use of state-of-the-art ‘magnetofection’ strategies [50]

  • Despite the key advantages offered by multimodal MNPs for OPC transplantation, there is a critical lack of neurocompatible and multimodal MNPs, representing a major scientific and commercial gap

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Summary

Introduction

OPC transplantation therapies for regenerative neurology Oligodendrocyte precursor cells (OPCs) are proliferative, stem-like cells of the central nervous system (CNS) that have emerged as a key transplant population to promote repair of myelin (the protective, fatty insulating sheath around nerve fibers) [1]. Five weeks post-transplantation into adult rat spinal cord, these cells were detected using ex vivo MRI demonstrating migration (up to 5 mm), with good correlation between MRI contrast, iron staining and transgene expression [32] From these studies, there is insufficient data to reach conclusions regarding the potential physicochemical basis for the different labeling results obtained with dextran coated MNPs in OPCs, as properties such as size and zeta potential differ substantially between the studies, or are entirely unreported. Purpose designed multimodal MNPs could mediate cell imaging, genetic modification and magnetic cell targeting One such multimodal MNP was recently described, with high iron content for MRI contrast (and possibly cell targeting), a fluorophore for histological detection, and potential for gene delivery which was demonstrated in astrocytes – a major neural transplant population [54]. Whilst our previous work showed that the gene delivery capacity of the particles was low overall (

Conclusions
25. Wang Y-XJ: Superparamagnetic iron oxide based MRI contrast agents
53. Jenkins SI
65. Hohnholt MC
Findings
69. Franklin RJM
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