Cells hanging in a magnetic field feel at home

Phages suspended iron cells in a magnetic field
Membrane based on materials ScienceDaily:
3-D Cell Culture: Making Cells Feel Right at Home, Suspended in Magnetic FieldsAmerican doctors have learned how to grow human body cells levitating in a magnetic field.

To do this, they needed to put together several previously created technologies.

The new technique is designed to facilitate drug testing and the study of cancerous tumors, as, according to scientists, it helps cells "feel at home."

No matter how you look at it (literally and figuratively), you can't grow a liver, a heart, or even individual tissues in a Petri dish. Because it is flat, and in such conditions the biological material behaves inadequately, the observed phenomena do not correspond to those that occur inside the body.

So scientists are trying to create a three-dimensional matrix for tissues and organs, inventing a variety of volumetric Petri dishes. The current work has continued this direction.

A method for controlling cells of a living organism suspended in a liquid using a magnetic field was developed by biologists from Rice University and the Anderson Cancer Center at the University of Texas (MD Anderson Cancer Center).

Glauco Souza and his colleagues tried to arrange cells in three-dimensional space without any improvised devices and microscopic scaffolding. They lifted the cells from the bottom of the vessel using a magnetic field.

To do this, scientists made a hydrogel based on a polymer that contained gold nanoparticles with a diameter of 50 ± 8 nanometers and specially created phage viruses. They are believed to infect bacteria, but are safe for mammalian cells.

Left: it can be seen with the naked eye that during precipitation, the hydrogel captures iron oxide particles very well. On the right: a photo of a hydrogel obtained using dark field microscopy. Scale ruler – two micrometers (photo by Nature Nanomaterials).

These "nanocellulars", which American biologists call Au-phage-MIO, are capable of delivering specific loads to cells and organs. In this case, magnetite nanoparticles (Fe ₃ O ₄, with a diameter of 10-100 nm) became such a payload.

After living cells were added to the gel, the phages forced magnetic particles to penetrate inside them. It took several hours. Then the gel was removed, the culture was thoroughly washed, and then experiments using a magnetic field began.

It turned out that in order for the cells to begin to levitate and form a three-dimensional suspension in the nutrient fluid, it is enough to apply a weak field. A press release from Rice University mentions that the magnet used was comparable in size to a coin.

Diagram of the cell processing process (illustration by Nature Nanomaterials).

In such a suspended position, cells can live and multiply, spreading in all directions – this is more natural for them than living on the flat bottom of a cup. This means that in laboratory conditions they will function in the same way as in living nature.

To test this assumption, doctors conducted the following experiment: they took glioblastoma cells (brain tumors) and performed all the above manipulations with them.

The cells "sprouted" in a three-dimensional environment (after 72 hours, spheres with a diameter of one millimeter were formed) and began to produce the same proteins as in the mouse body. At the same time, in previous experiments in flat cups, nothing like this happened to cancer cells. Details can be found in the article of the authors of the development in the journal Nature Nanotechnology (Glauco R. Souza et al., Three-dimensional tissue culture based on magnetic cell levitation).

By moving the magnet and changing the intensity of the magnetic field, biologists have learned to vary the shape of "balls" from cells. This may be useful in the future when creating fabrics of different types. For example, the skin and nerve fibers grow differently, which means that they need to be "pulled" in different ways.

Micrographs of levitating glioblastoma cells obtained by transmission electron microscopy.
From left to right:
after 24 hours of cultivation, magnetite nanoparticles inside the cells are highlighted in black;
after 7 days, in the center of the spheres from the cells, the nanoparticles moved into the extracellular matrix;
also 7 days later, there were almost no nanoparticles left in the shell of the spheres.
The scale ruler is 5 micrometers (photo by Nature Nanomaterials).

"The beauty of this method is that it gives cells the opportunity to interact with each other, to build a three-dimensional structure of micro-tissues. The simplicity of the technology allows it to be used by any laboratory that is just starting to grow spatial cell cultures, by any scientific group interested in studying stem cells. The method can be used in regenerative medicine and biotechnology, as well as drug testing," says Robert Raphael, one of the researchers.

American scientists dream that sooner or later, with the assistance of their technology, tissues for transplantation and even whole human organs will be grown. But for now, the main application of the novelty is likely to really be testing of drugs and methods of treating malignant tumors.

"Cultures growing in three–dimensional space are more like real body tissues, respectively, they provide more reliable results of preclinical drug trials," says another author of the work Tom Killian. "Meanwhile, if you manage to improve the accuracy of the early drug screening procedure by at least 10%, you will save hundreds of millions of dollars on each drug."

Another advantage of the new method is speed. "Magnetic forces cause particles to stick together very quickly," notes George Whitesides from Harvard, who was not involved in this work. "If you test, for example, 100 thousand doses of drugs for toxicity on 100 thousand tissue samples, the time savings can be very significant," Killian echoes him.

Above: photos of suspended glioblastoma cells,
obtained by scanning electron microscopy,
24 hours after the start of the experiment and on the eighth day.
The scale ruler is 100 micrometers.
Below: cell fluorescence on the second day and after 12 weeks,
the latter demonstrates the viability of cells.
The ruler is 200 micrometers (photo by Nature Nanomaterials).

However, Whitesides also points out one of the disadvantages of the method, which is inherent, however, in all others: cells located in the inner part of any laboratory three-dimensional structures suffer from a lack of nutrients, oxygen and die quickly. Tom replies that he and his colleagues are already working on creating a solution that may solve this problem.

Another application of the novelty is the study of cancer. Malignant tumors grown on an "invisible matrix" created by a magnetic field are also more similar to those that grow in the human body. This in itself is a great achievement, adds another researcher Wadih Arap (Wadih Arap).

Soudza's team is currently conducting additional tests-comparing existing methods of growing three-dimensional matrices from cells and new magnetic technology. So far, Glauco is confident that this development will show exactly the same, if not better results.

By the way, the start-up company Nano3D Biosciences, which now owns a license to create a magnetic gel, will further commercialize the method. It is reliably known that it has already come up with a simple and understandable name for the future device – Bio-Assembler ("Bio-Collector"). Probably, it will soon be offered to all laboratories wishing to try out a new unusual method of growing tissues.

Portal "Eternal youth" http://vechnayamolodost.ru22.03.2010