Table 2 Challenges for cell transplantation therapies and the relevant utility of magnetic nanoparticles

Clinical needs

• Therapeutic biomolecule delivery for combinatorial therapies.

• Assess on-target/off-target delivery.

• Deliver high number of cells to lesions.

• Assess survival, differentiation, integration into host.

• Transgenes more effective than separate biomolecule delivery.

• Correlate clinical improvement/side-effects with cell presence.

• Reduce cell loss/maximize therapeutic effect.

• Correlate biodistribution of cells with evidence of regeneration.

• Minimize off-target effects.

Current methods

• Viral vectors efficient but raise clinical safety concerns and require substantial infrastructure.

• Plasmonic resonance of gold nanoparticles: promising, but little infrastructure; gold particles cannot be non-invasively manipulated.

• Invasive injection into lesion parenchyma risks secondary damage.

• Dyes frequently leak and label host cells.

• Many nonviral methods inefficient, unsafe and/or not clinically relevant.

• Radiation exposure is associated with CT scans (X-rays) and PET scans (tracers).

• Distal intravenous/intrathecal delivery limits adherence/accumulation at target.

• LacZ transgene expression confounded by host microglial β-galactosidase activity.

• Cell-seeded scaffolds require invasive delivery at lesion site.

• Mismatched gender/species/mutant transplants are not clinically relevant.

Benefits of MNPs

• Comparable efficiency to other nonviral systems.

• Provide contrast for non-invasive MRI.

• Non-invasive manipulation of MNP-labeled cells using magnetic fields for:

• Provide MRI contrast.

• Safe protocols developed.

• Clinical MRI equipment and expertise widely available.

• Retention of cells at target site, facilitating adhesion.

• Metals (e.g. iron) can be stained.

• ‘Capture’ of cells from blood/cerebrospinal fluid; safe delivery distal to lesion.

• Fluorophores can be incorporated into MNPs (for preclinical testing).