Cells on Ice

Engineering team prepares for the day when stem cells win public acceptance

Photo: Michael Dumiak

Cryo-Engineer

Heiko Zimmermann pulls a sample rack from a liquid nitrogen tank at the Fraunhofer Institute for Biomedical Engineering in St. Ingbert.

Picture a world in which stem cell research is uncontroversial and regenerative medicine is ubiquitous. Many millions of people will want to store cell specimens, for use in all manner of contingencies. This may sound far-fetched under current circumstances, but it’s the vision of the future motivating a group of German ­researchers who are developing an automated industrial-scale cell archive, in which millions of cell specimens can be frozen for decades, waiting to be reanimated when needed.

The challenges facing Günter Fuhr’s team at the Fraunhofer Institute for Biomedical Engineering, in St. Ingbert, are to create a robust and secure data system that operates under supercold conditions, to design a compact storage area for the cell samples themselves, and to figure out how to securely and precisely automate the handling of these precious specimens. The scientists have some advanced technology and the natural logic of industrialization on their side, but they face an uncertain marketplace and persistent public controversy.

While stem cell research may not be quite the hot-­button issue in Germany that it is in the United States, concerns about privacy and personal data management are far more acute because of the country’s police-state history.

The Fraunhofer bioengineering laboratory is located in a sleepy valley, about 165 kilometers west of Frankfurt, on the French border. The day Fuhr and his colleagues made themselves available to a visiting reporter, there was an early morning chill and not much was moving; coffee drinkers grumbled in the 1950s-era train station café. Nobody was on the sidewalks, and the town looked like an old postcard—except for clouds of condensation billowing out from a liquid-nitrogen truck, outside the institute.

Upstairs in the building, the scientists are sitting on leather-and-chrome sofas. At present, explains the 53-year-old Fuhr, tiny cell samples can be frozen at –130 °C, stored in tanks for years, thawed, and reanimated. This procedure is commonplace in research labs, but it has not been done on a large scale—the objective sought at the lab.

Conventionally, cell samples are stored in cryotanks in small vials; the data on the samples are stored electronically outside the tank, sometimes matched with bar code ­stickers inside. A more secure and robust procedure, as Fuhr and his colleagues see it, would be to keep the data with the cells in the deep freeze.

To do the job, they developed cell-storage units that look like flat punch-out pill ­packets, each with its own memory chip that can store video and microscopic pictures of the sample, instructions on how it should be handled, and sensitive legal documents. The units are arranged in a grid on stacked trays, which connect by standard USB or FireWire cable to central controls. (In  the future, such connections may be made wireless.)

A person’s cell samples would be subdivided, so that small sections could be popped out, defrosted, and used as needed, without having to unfreeze and refreeze the whole sample.

Key to the procedure is the flash memory chip, says Fuhr’s cryobiophysics department head, Heiko Zimmermann [see photo, ”Cryo-Engineer”]. It is an off-the-shelf compact IC that has been modified to work in extreme cold. Locating all relevant information directly with the specimen obviates central storage of vast amounts of highly personal information, eliminates the possibility of mismatches between central databases and samples, and facilitates automated handling and manipulation of samples.

In principle, the lab has space to store 100 million cell samples—enough to accommodate samples of stem-cell-rich umbilical cord blood from every new German born. But that won’t start happening tomorrow. Stem cell research in Germany is not a major front in the culture wars the way it is in the United States, but it is still a sensitive issue. In part that’s because of the Catholic Church’s influence in the southern and western parts of the country, but also, just as important, it’s because of concerns connected with memories of Nazism and the Holocaust. Centralizing personal medical tissue and data in a large cell farm would raise red flags in Germany, if only because centralizing any personal data, especially genetic data, causes alarm here.

There are also practical concerns that could inhibit acceptance of a large cell archive. For example, researchers and medical workers typically want to be close to their samples, not to have to travel far to get to them.

Fuhr’s immediate aim is to run a research cryobank and license its technology, know-how, and development work to private industry. His expectation is that stem cell and regenerative medicine will not be bogged down in debate forever. ”When tissue engineering gets started, then you need a lot of samples,” Fuhr predicts. Even if, say, only a small fraction of the people in a big country wished to have the possible benefits of regenerative medicine made available to them, millions of cell samples would have to be archived.

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