From the Labs: Biomedicine

Cellular Fusion
A microchip efficiently pairs cells to create hybrids

Source: “Microfluidic control of cell pairing and fusion”
Joel Voldman, Rudolf Jaenisch, et al.
Nature Methods 6: 147-152

Results: A microfluidic chip designed by scientists at MIT efficiently traps different cell types and pairs them so that they can be fused into hybrids, a technique that is commonly used to study biological processes and can also be used to “reprogram” cells. The chip produced successfully fused hybrids five times more efficiently than commercially available devices do.

Why it matters: Fusing a stem cell to a differentiated adult cell can cause the adult cell to revert to an earlier developmental state; this reprogramming is one of the most exciting advances in stem-cell research, making it possible to generate stem cells from adult cells rather than embryonic ones. To ­better understand this phenome­non, researchers need a way to easily fuse large numbers of cells. The new technology will allow scientists to study the process in greater detail, perhaps enabling them to reprogram cells more efficiently.

Methods: The researchers built a two-square-millimeter chip dotted with tiny structures designed to trap cells. One side of each trap can hold no more than one cell, and the other side can hold two cells. When the researchers inject a solution containing cells into the chip, some of the cells are trapped on the one-cell side. A second squirt of fluid moves the captured cells to the side of the trap that holds two cells. Next, a solution containing a second cell type is injected into the device, and the two cell types are captured together. Finally, an electrical jolt delivered to the device fuses the two cells’ membranes.

Next steps: The researchers plan to study how adding different proteins to the cell-containing solutions affects the efficiency of fusion and reprogramming.

Source: “A tunable synthetic mammalian oscillator”
Martin Fussenegger et al.
Nature 457: 309-312

Results: Scientists at the Swiss Federal Institute of ­Technology Zürich genetically engineered a molecular oscillator that turned the production of a fluorescent protein in a hamster cell on and off every two to three hours for more than 20 hours. Changing the amount of DNA added to the cells varied the frequency of the oscillations.

Why it matters: Genetic oscillators could have numerous applications in genetic engineering and drug delivery. The clock might be adapted to deliver a protein drug; the frequency and amplitude of the oscillations would determine the dose of the drug and how often it was delivered. The findings may also help scientists understand the molecular clocks mediating numerous biological functions, such as circadian rhythm.

Methods: Researchers modified the hamster cells with DNA containing the code for a specific gene and the complement of that code. Turning on that gene creates an RNA transcript for a transcription factor, a protein that in turn activates production of a fluorescent protein and a second transcription factor. An excess of the second transcription factor activates the complementary code, which produces the mirror image of the original RNA transcript. This mirror transcript binds to the original RNA transcript, stopping the production of the fluorescent protein and the second transcription factor. Without the second transcription factor, the mirror transcript is no longer produced, and the concentration of the regular gene transcript begins to build again.

Next steps: The researchers are now trying to get the oscillator to function synchronously in an entire population of cells, which will be necessary if it is to be used for drug delivery.