Scientific Method —

DNA used as velcro to form cells into 3D structures

An alternative to 3D printing a tissue.

One of the great hopes for stem cells is that they'll allow us to eventually replace injured or damaged tissues. But there's a big gap between the cells of stem cells and anything resembling an organ. Organs are complex, three-dimensional structures populated by multiple cell types. Getting a bunch of cells to form these structures is a significant challenge.

One idea has been to use 3D printers. With multiple print-heads and a protein polymer gel, it's possible to construct a rough approximation of the structure of a mature organ. Now, a team of California scientists has come up with an interesting alternative: use DNA as a sort of cellular velcro to get cells to stick to each other and form a complex, three-dimensional tissue.

The basic idea is pretty simple. If they have the appropriate sequences, individual DNA molecules will pair up to form a double helix. If you coat one cell type with a short DNA sequence and then a second cell type with the sequence's partner, the two cells will stick to each other. And it's possible to coat a cell's surface with DNA simply by adding a lipid molecule to the end of the DNA strand.

To get the process started, the researchers used a standard 2D printer to coat specific areas of a microscope slide with DNA. Then they coated some cells with that DNA's complement and floated them across the slide, which caused them to stick in the pre-defined pattern.

It's possible to print different sequences on the slide, allowing different populations of cells to stick in a more complex pattern. It's also possible to build the cells up by coating a second population of cells with a DNA sequence that allows them to stick to the first population of cells. Combined, the two techniques can produce some pretty complicated structures.

(The authors have posted a time-lapse movie of the process as part of their supplemental data.)

Once the cells are in place, the authors cover them in a protein solution that slowly solidifies to form a gel that the cells are happy growing in. (It's a bit like a simplified extracellular matrix.) As they grow, they can organize and form contacts with each other, eventually forming a coherent tissue.

It's important to note, however, that the authors only test this with cell types that tend to naturally form coherent tissues if put in the right environment. Not all cell types are quite that cooperative.

And there are trade-offs. 3D printing probably allows finer control and construction of more complicated structures. But the cells are squirted out of the print heads at random, meaning that their density is going to vary quite a bit. That may limit their ability to interact and organize. Here, while the structures probably aren't as complicated, the cells necessarily start out in contact with each other, making it a bit easier for them to self-organize.

In any case, this sort of technology is at its infancy, and it's not clear whether any of it will work out the way we hope it will. It's nice to have options, since it's likely that one of them will work out well enough to get us what we need.

Nature Methods, 2015. DOI: 10.1038/nmeth.3553  (About DOIs).

This post originated on Ars Technica

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