Biomedical Engineering Reference
In-Depth Information
and endothelial progenitors (Lee et al.
2010b
). Despite the apparent ability to label
virtually any cell type, the detection of target cells has been restricted by the number
of particles taken up. The quantity of iron oxide attached to a cell is a direct deter-
minant of cell detectability. With a greater amount of iron oxide loading per cell,
there is less emphasis on hardware requirements and imaging duration to achieve
the required SNR and resolution for cellular detection (Heyn et al.
2005
).
Labelling appears to be relatively harmless to the cells - cell survival, proliferation,
function and even differentiation are usually minimally affected, provided the intra-
cellular iron load is not excessive. Although high concentrations of particles in the
culture medium increases cellular iron quantity, excessive concentrations have also
been associated with free radical generation, decrease in cell proliferation, apoptosis
(van den Bos et al.
2003
) and decrease in motility (Nohroudi et al.
2010
). Cell
labelling can be achieved by binding iron oxide particles onto the cellular surface
or by incorporating them into the intracellular space. The latter method is favoured
as particles at the cell surface can hinder cell-cell interaction by blocking cell surface
receptors. Even when particles are internalised, it is important that they do not alter
the properties or functions of the cell, particularly with high amounts of iron loading.
Hence, labelled cells are often compared with intact cells in terms of viability,
proliferation, gene expression, and in addition, the differentiation capacity for stem
cells (Lee et al.
2009
; Balakumaran et al.
2010
).
The quantity of iron oxide particles internalised by cells, typically expressed as
picograms of iron per cell, determines their MR detectability. High iron loading can
thus relax the hardware requirements to detect low cell numbers. When labelling
phagocytic cells like macrophages, large amounts of iron loading (61 pg/cell) can
be achieved with clinically-available SPIO (Heyn et al.
2006
). However, labelling
of non-phagocytic cells such as MSC with SPIO has been less efficient, with
approximately only 9 pg/MSC (Mailander et al.
2008
), and may require alterations
of the labelling method to achieve higher iron loading.
Iron oxide loading of cells can be increased by using particles with high content of
iron oxide, a characteristic that depends on the synthesis method. The internalisation
of particles is also affected by the interaction at the particle-cellular interface, which
is determined by the physicochemical properties of the particles (chemical compo-
sition, size/geometry, surface charge, coating/ligands, aggregation status), the cell type
(professional phagocytes versus other cell types), as well as the labelling medium.
4.1
Particle Surface Composition and Charge
The iron oxide particles in biomedical applications are often coated with dextran or
other formulations. The coating material, at times carrying electrostatic charges, can
mediate both inter-particle and particle-cellular interactions. While in a dispersing
medium, particles are in Brownian motion due to random collision from water mole-
cules, where they experience both interparticle attractive and repulsive forces. When
attractive forces, such as van der Waal's forces or magnetic dipole-dipole interactions
from residual magnetic moment dominate, the particles form irregular aggregates.
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