A team of chemists at UC Berkeley managed to create artificial microtissues capable of performing basic tasks like fluid secretion and reacting to hormones. The new technology may form a building block for a whole array of artificial tissue engineering of the future.
From a Berkeley press release:
Gartner [Zev J. Gartner] and Bertozzi [Carolyn Bertozzi] assembled three types of cultured cells into onion-like layers by using two established technologies: DNA hybridization and Staudinger chemistry. DNA hybridization is like a “programmable glue,” she said, that can stick cells together because of the highly precise nature of binding between complementary DNA strands: One strand of the DNA helix binds only to its complementary strand and nothing else. By putting a short DNA strand on the surface of one cell and its complementary strand on another cell, the researchers assure that the two lock together exclusively.
To get these specific DNA strands onto the cells, they used chemical reactions that do not interfere with cellular chemistry but nevertheless stick desired chemicals onto the cell surface. The technique for adding unusual but benign chemicals to cells was developed by Bertozzi more than a decade ago based on a chemical reaction called the Staudinger ligation.
After proving that they could assemble cells into microtissues, Gartner and Bertozzi constructed a minute gland – analogous to a lymph node, for example – such that one cell type secreted interleukin-3 and thereby kept a second cell type alive.
“What we did is build a little miniaturized, stripped-down system that operates on the same principle and looks like a miniaturized lymph node, an arrangement where two cells communicate with each another and one requires a signal from the other,” she said. “The critical thing is that the two cells have to have a cell junction. If you just mix the cells randomly without connection, the system doesn’t have the same properties.”
She expects that eventually, clusters could be built on clusters to make artificial organs that someday may be implanted into humans.
“Our method allows the assembly of multicellular structures from the bottom up. In other words, we can control the neighbors of each individual cell in a mixed population,” she said. “By this method, it may be possible to assemble tissues with more sophisticated properties.”
One interesting aspect of the technique is that DNA hybridization seems to be temporary, like a suture. Eventually, the cells may substitute their own cell-cell adhesion molecules for the DNA, creating a well-knit and seemingly normal, biological system.
Full story: Assembling cells into artificial 3-D tissues, like tiny glands…
Images: Top: Short, complementary strands of DNA (oligonucleotides) are attached to two different cells and hybridize to bring the cells into physical contact. By using different complementary DNA strands, it is possible to build microtissues of three or more cell types. Side: A 3-D reconstruction using deconvolution fluorescence microscopy of a single multicellular structure encapsulated in agarose gel. Cells are stained different colors according to the oligonucleotide sequence attached to their surfaces. (Bertozzi lab/UC Berkeley images)