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Table 1 Comparative data from MNP studies involving OPCs or oligodendroglial cell lines

From: Magnetic nanoparticles for oligodendrocyte precursor cell transplantation therapies: progress and challenges

Ref

Particle

Core (nm ± SD)

Surface

Size (nm ± SD)

Zeta (mV ± SD)

Cell type

Uptake/Labeling/Transfection [incubation conditions]

Transplant

MRI

Toxicity/comments

[29]

MION-46 L (CMIR, USA)

EM: 4.6 ± 1.2; maghemite or magnetite

Dextran

DLS: 8-20

-2.0 ± 0.4 (H2O)[44]

CG4

None [48 h; 50–500 μg Fe/ml]

n/a

n/a

No data supplied

 

MION-46 L-OX-26

 

Dextran + anti-Tfr antibody OX-26c

Not tested

Not tested

 

“numerous intracellular vesicles”, not quantified [48 h; 2–50 μg Fe/ml]

Myelin deficient (md) rat spinal cord, P7.

Post-mortem excised spinal cord, 14 d; MRI contrast correlated well with iron-staining and new myelin

Trypan blue assay: similar viability for labeled/unlabeled cells

[30]

SPIOa

2-7d

Dextran

Not tested; <400e

Not tested

CG4

>60% of cells labeled [24 h; 2 μg Fe/ml]

Adult rat ventricles

Labeled cells detected, post-mortem excised brain, 7 d

No data supplied

[45]

MD-100a

EM: 7-8; maghemite or magnetite crystals; multiple per particle

Carboxylated dendrimers

SEC: 20-30[46]

Not tested; “highly polarized”; carboxylation implies negative

Primary rat NSC-derived OPCs (LacZ+)

“remarkable high degree of intracellular labeling”; within vesicles/endosomes; relaxometry: 9.3 ± 4.3 pg Fe/cell; Ferrozine: 8.5 ± 2.0 pg Fe/cell [48 h; 25 μg/ml]

Long-Evans Shaker (les) rat ventricles, P0

In vivo, 6 weeks post-transplantation; ‘excellent’ MRI contrast correlation with LacZ expression post-mortem

Labeled cells viable. No difference in growth between labeled/unlabeled cells

[31]

MD-100a

    

CG4

10 pg Fe/cell (control: 1 pg); retained at 1 week in vitro [24–48 h; 10–25 μg Fe/ml]

n/a

n/a

Proliferative capacity and viability unaffected

      

Primary rat NSC-derived OPCs (LacZ+)

10 pg Fe/cell; retained at 1 week in vitro [24–48 h; 10–25 μg Fe/ml]

Long-Evans Shaker (les) rat ventricles, P0

In vivo, 6 weeks post-transplantation; ‘excellent’ MRI contrast correlation with LacZ expression post-mortem

Proliferative capacity and viability unaffected

[33]

Feridex (Berlex, USA)

5; iron oxide

Dextran

DLS: 50-180

-31.3 (H2O)

CG4

low” [48 h; 25 μg Fe/ml]

n/a

Labeled cells detected in gelatin

No data supplied

 

Feridex + Lipofectamine

 

Dextran + Lipofectamine Plus

Not tested

Not tested

 

14.7 ± 1.7 pg Fe/cell (control: 1.9 ± 0.9) [48 h; 25 μg Fe/ml]

   
 

Feridex + PLL

 

Dextran + PLL

Not tested

Not tested

 

3.8 ± 1.2 pg Fe/cell [48 h; 25 μg Fe/ml]

   

[32]

Feridex (Berlex, USA) + PLL

5; iron oxide

Dextran + PLL

DLS: 50-180

-31.3 (H2O)

Primary rat GRP + NRP (transgenic)

“large numbers of particles were taken up”; localized to endosomes, not nuclear; [48 h, 25 μg Fe/ml]

Adult rat spinal cord

Labeled cells detected, post-mortem excised spinal cord, 5 weeks post-transplantation; 5 mm migration. MNPs correlated well with iron-staining and transgene expression.

Transplanted cells differentiate comparably to unlabeled cells. Labeled transplants elicited greater immune response.

[47]

Fe-NPa

5-20; maghemite

Citrate

Not tested

Not tested

OLN-93

159 ± 34 nmol Fe/mg protein, ~2.2 pg Fe/cellf (control: 10 ± 2, ~0.1 pg Fe/cellf); concentration-dependent; in intracellular vesicles [48 h; 300 μM]

n/a

n/a

No effects on viability, morphology or proliferation. No Fe leaching from MNPs.

[48]

D-IONPa

5-20; iron oxide

DMSA

DLS: 60

-26 ± 3 (FCS-)

 

4200 nmol Fe/mg protein, ~57 pg Fe/cellf (control: 7, ~0.1 pg Fe/cellf); concentration-dependent; retained at 24 h [8 h; 4 mM Fe]

n/a

n/a

Concentration-dependent: altered morphology, increased ROS, decreased GSH, but all reversible and viability unaltered.

[49]

D-IONPa

     

957 nmol Fe/mg protein, ~13 pg Fe/cellf (control: 5, ~0.1 pg Fe/cellf); decreased to ~620 nmol Fe/mg at 48 h, ~8 pg Fe/cellf; concentration-dependent; perinuclear accumulation [24 h; 1000 μM; 55 μg Fe/ml]

n/a

n/a

None evident. No ROS increase. Increased ferritin.

[50]

Neuromag (OZ Biosciences, France)

Not tested; ~0.5% Feb

Not tested; proprietary

DLS: ~216[51]

Not reported; proprietary

Primary culture-derived OPCs

~21% of cells transfected [oscillating magnetic field; 24 h]

Ex vivo, onto organotypic neural tissue slice

n/a

None evident by morphology or cell counts. ‘Transplanted’ cells proliferated, differentiated, integrated into slice.

[52]

Sphero (Spherotech, USA)

Not tested; Polystyrene, nile red-stained

Carboxylated Fe3O4/ polystyrene; 15-20% Feb

EM: 200–390 (mean 360);b DLS: 843-961

-14.3; -23.13b

 

~60% of cells labeled; heterogeneous extent, typically ‘low’. Time- and concentration-dependent. [24 h; 50 μg/ml]

n/a

Particles in agar gel show concentration-dependent contrast

None evident by morphology or cell counts. Generated MNP-labeled oligodendrocytes. Intracellular MNPs appear stable.

[53]

Fe3O4-PEI-RITCa

EM: 24.3 ± 5.7; XRD: 25.5; Fe3O4; ~58% Fe[54]

1800 MW PEI; RITC[54]

Not tested

+18.6[54]

 

~50% [5 μg/ml], ~60% [24 h; 20 μg/ml]. Concentration-dependent.

n/a

Particles show concentration-dependent contrast

None evident by morphology or cell counts

[55]

D-IONPa

EM: 4-20

DMSA

DLS: 53 (H2O); 52 ± 2 (medium, FCS-)

-58 ± 4 (H2O); -20 ± 10 (medium, FCS-)

OLN-93

Specific iron: ~1700 nmol/mg protein, ~23 pg Fe/cellf (~30-50% represents extracellular MNPs; control: 69 nmol/mg, ~1 pg Fe/cellf) [FCS-; 4 h, 1 mM]

n/a

n/a

Unaltered LDH activity

    

DLS: 109 ± 23 (medium, FCS+)

-9 ± 1 (medium, FCS+)

 

201 ± 63 nmol/mg protein, ~3 pg Fe/cellf [FCS+]

   
 

BP-D-IONPa

EM: 4-20

DMSA + BODIPY

DLS: 63 (H2O); 61 ± 5 (medium, FCS-)

-58 ± 18 (H2O); -28 ± 2 (medium, FCS-)

 

Specific iron: ~1800 nmol/mg protein, ~24 pg Fe/cellf (~30-50% represents extracellular MNPs; control: 69 nmol/mg, ~1 pg Fe/cellf); Not lysosome-associated. [FCS-; 4 h, 1 mM]

n/a

n/a

Unaltered LDH activity

    

DLS: 138 ± 24 (medium, FCS+)

-10 ± 1 (medium, FCS+)

 

171 ± 15 nmol/mg, ~2 pg Fe/cellf [FCS+]

   
  1. aIn-house synthesis; bManufacturer supplied data; cInternalizing anti-transferrin receptor monoclonal antibody; dBased on patent PCT/JP93/001092; eNot reported, but measurements of electron micrograph in article suggest <400 nm (could be MNP aggregate); fpg Fe/cell values not reported but calculated as per Additional file1; CG4 = oligodendroglial cell line; DIV = days in vitro; DMSA = dimercaptosuccinic acid; DLS = dynamic light scattering; EM = electron microscopy; FCS = fetal calf serum; GFP = green fluorescent protein; GRP = glial restricted precursor; GSH = glutathione, antioxidative molecule; LacZ = gene encoding β-galactosidase; LDH = lactate dehydrogenase; MBP = myelin basic protein, oligodendrocyte marker; NRP = neuronal restricted precursor; NSC = neural stem cell; OLN-93 = oligodendroglial cell line; OPC = oligodendrocyte precursor cell; PEI = polyethyleneimine; PLL = poly-L-lysine; RITC = rhodamine B isothiocyanate; ROS = reactive oxygen species; SEC: size exclusion chromatography; Tfr = transferrin receptor; XRD = powder X-ray diffraction.