In preclinical drug discovery
validation processes, monolayer cell cultures are still predominant.
Nevertheless, 2D cultures can only mimic the conditions of physiological
tissue to a limited extent, whereas cells in vivo are able to interact
in a three-dimensional network. Therefore, results generated from 2D
cultures may often be of limited relevance for clinical effectiveness
and may contribute to high attrition rates in the drug development
process. The employment of spheroid cultures is regarded as a better
rational to develop more predictive in-vitro screening assays for
preclinical drug development, especially in cancer research.
In spheroid cultures, cells grow in a
three-dimensional system with zones of cellular heterogeneity and
nutrient and oxygen gradients, to more closely reflect the in-vivo tumor
microenvironment. Comparisons of spheroid cultures and 2D monolayer
cultures showed functional differences in tumor cell lines, e.g.
alterations in protein expression, phosphorylation patterns and
responsiveness to inhibitor molecules.
Magnetic 3D Cell Culturing – The n3D Approach
The
core technology of our partner Nano3D Biosciences (n3D) is the
magnetization of cells with NanoShuttle™-PL. The cells can be aggregated
with magnetic forces, either by levitation or printing, to form
structurally and biologically representative 3D models in vitro.
The advantages of magnetic cell culture include:
Mimicking native tissue environment
Rapid 3D model formation within hours
No specialized equipment, media, or artificial substrate
Easy to handle / no sample loss
Allows co-culture
With magnetized spheroids, solution addition and removal is made
easy by using magnetic force to hold them in a stationary position
during aspiration, thereby limiting spheroid loss. Spheroids can also be
picked up and transferred between vessels using magnetic tools such as
the MagPen™
With magnetized spheroids, solution
addition and removal is made easy by using magnetic force to hold them
in a stationary position during aspiration, thereby limiting spheroid
loss. Spheroids can also be picked up and transferred between vessels
using magnetic tools such as the MagPen™.
NanoShuttle™-PL consists of gold, iron
oxide, and poly-L-lysine. NanoShuttle™-PL magnetizes cells by
electrostatically attaching to cell membranes during an overnight static
incubation. Magnetized cells will appear peppered with dark
nanoparticles after incubation. NanoShuttle™-PL will stay attached to
the cell membrane for up to 8 days, at which point it’s released into
the 3D culture. NanoShuttle™-PL is biocompatible, having no effect on
metabolism, proliferation, and inflammatory stress, and even encouraging
proliferation in 3D. Additionally, it does not interfere with
experimental techniques, such as fluorescence, or Western blotting.
