Table 1: Summary of in vitro studies performed in recent years highlighting commonly used assays aimed at investigating toxicity of SPIONs on stem cells and the results.

Particle usedBiological polymerParticle sizeCells typeParticle concentrationToxicity assayResultReference

Feridex (FDA approved) Dextran80–150 nmrMSC & mMSC25 μg/mLLive/dead (7 days after labelling) differentiation
No loss of cell viability observed after 7 days with or without either TA[32]
Ferric oxide (noncommercial) Poly-L-lysine15 nmHUC20 μg/mLMTT (5 days continued culture) cellular
apoptosis—annexin V/PI double stainassay
NoncommercialSilica110 nmhMSCs200 μg/mLMTT ( 1 hr and 24 hrs)
Trypan Blue
No reduction in viability after 1 hour. No
reduction in cell proliferation
FeridexDextran80–150 nmhMSC100 μg/mLFACS ( fluorescence-activated cell sorting) to
evaluate cell death—to determine if iron oxide
incorporation affects surface markers expression
No reduction in viability after 12 hours[39]
Iron fluorescent particlePolystyrene 900 nmpMSCTrypan Blue
Morphological observations
Differentiation studies
Cells maintained viability and retained label for up to 3 months. Differentiation capacity not
Manganese oxide nanoparticlesMesoporous silica65 nmmMSCsMTS 75% cell viability
Limited cell differentiation in the osteogenic lineage
Commercially available1630 nmrMSCs2.8 μg/mLTrypan BlueDid not affect cell viability[41]
FeridexDextran150 nmESCs50 μg/mLTrypan Blue Did not affect cell viability[42]
HEDP rMSC25, 50, 100 μg/mLMTSCell viability not affected at lower concentrations but viability decreased to 70% at 100 μg/mL[43]
Feridexuncoated80–150hMSC50–250 μg/mL Comet assay Did not affect viability[44]

rMSC: rat mesenchymal stem cells; mMSC: mouse mesenchymal stem cell; hMSC: human mesenchymal stem cells; pMSC: porcine mesenchymal stem cells; HUC: human umbilical cells; HEDP: hydroxyethylidene bisphosphonic acid.