Stem Cells In Action

From Madison, They’re Shipped To Disease-fighting Researchers
The Only Official Repository Of The Cells In The U.S. Expects To Get Almost All Of Its Remaining Deposits Soon.

September 23, 2007
by David Wahlberg
Wisconsin State Journal

Freezers, flanked by tanks of liquid nitrogen, line a wall. Shipping containers, resembling kid brothers of R2D2, sit on shelves.

It’s not an unusual scene for Madison’s University Research Park.

But this equipment contains unusual cargo: government-sanctioned human embryonic stem cells.

Two years after the National Institutes of Health created the National Stem Cell Bank, managers say the bank is starting to fulfill its mission: gathering the cells in one place, controlling their quality and shipping them to scientists at low cost.

Housed at the WiCell Research Institute, affiliated with UW-Madison, the country’s only official repository of the cells expects to receive nearly all of its remaining deposits soon.

WiCell analyzes and grows the cells, which have been extracted from days-old embryos leftover from fertility clinics. Then it sends the cells around the world to researchers, who hope to turn them into cures for diabetes, spinal-cord injury, heart disease, Parkinson’s disease and other conditions. The blank-slate cells are thought to be capable of becoming all of the body’s 220 cell types.

In October 2005, the NIH granted WiCell $16 million over four years to test, store and distribute 21 stem-cell lines, or colonies. They are the only such cells available for federal funding under President Bush’s stem-cell policy established in 2001.

A San Diego company contributed three lines this month. That gave the bank 15 lines, including five created by UW-Madison researcher James Thomson. Other companies are expected to deliver five lines by the end of the year.

Each cell line arrives at WiCell frozen inside about 15 vials, each vial containing roughly 3 million cells.

Scientists – about two dozen of them at WiCell and another dozen at labs on campus – subject the cells to months of rigorous testing. WiCell also ships cells to labs outside of the state for some tests.

The scientists work under sterile hoods controlled by filters and special air flow. They analyze the cells’ genetic characteristics, screen for deadly viruses, study cell signals and assess whether each line is better suited for research on blood, the heart, the pancreas or the brain.

About 30 tests are performed on each cell line.

It’s the seemingly simple step of thawing the cells, before the testing begins, that most gives workers the jitters. The fragile cells are most vulnerable when emerging from their deep freeze. One misstep and they could die.

“It’s like cutting a diamond when you thaw that first vial,” said Derek Hei, director of the stem-cell bank. “These cells have historical value. They are not replaceable.”


Progress at the stem-cell bank initially appeared to be slow. For nearly a year after receiving the NIH grant, WiCell had only Thomson’s five cell lines and five contributed by ES Cell International, of Singapore.

Several factors may have contributed to the delay, WiCell managers say, including the competitive nature of the science.

An example of that has been a battle over three patents on Thomson’s cells held by the Wisconsin Alumni Research Foundation, UW-Madison’s tech-transfer arm. WiCell is a subsidiary of WARF.

Critics say licensing fees charged under the patents by WiCell are impeding research and driving scientists overseas.

Consumer watchdog groups from California and New York asked the U.S. Patent and Trademark Office last year to review the patents. The patent office preliminarily rejected the patents this spring. A final ruling, expected soon, likely will be appealed in court.

Sue Carlson, WiCell’s director of operations, said some stem-cell line owners didn’t hand over their cells quickly because they were skeptical of how the bank would operate.

“We had to prove ourselves,” she said. “It takes a while to gain their trust.”


Recent activity suggests the bank has become trustworthy, Carlson said.

The University of California, San Francisco, contributed two lines in September 2006. Novocell, of San Diego, delivered three lines this month.

Technion, of Israel, recently agreed to deposit its three lines, said Andy DeTienne, a licensing manager for WARF and WiCell. Cellartis, of Sweden, is “working toward a signature” regarding its two lines, DeTienne said.

The remaining line is owned by ES Cell International, which already contributed its five other lines. It’s not clear if or when its last line might arrive.

WiCell managers say they may end up with 20 lines instead of 21. But they still consider that a “full” bank.

“We’re going to have 100 percent of the cells under agreement soon,” DeTienne said. “I think that’s great progress.”

All 20 lines, once they are grown and tested, should be available to researchers within a year, he said.

Hei said WiCell will make public the results of tests conducted on each line, so researchers can order cells best suited to their studies.

WiCell, through its NIH grant, prepares and ships the cells for $500, far less than what the owners of the lines would have to charge to recoup their costs, Carlson said.

WiCell has sent 464 shipments of cells to more than 270 scientists in 24 countries, she said. About 95 percent of those have been WiCell’s own cells, created by Thomson, but the proportion of other cells shipped likely will grow now that they are being received by WiCell, Carlson said.


The stem-cell bank’s future is uncertain, primarily for two reasons: The next president could loosen Bush’s policy, and that could increase the demand for newer stem-cell lines.

Bush’s policy said embryonic stem-cell research can receive federal funding only if it involves cell lines created before Aug. 9, 2001. Bush and many religious conservatives say it’s wrong to destroy even early-stage embryos for research because they consider them human life.

The 21 lines slated for WiCell’s bank are the only viable cells that qualify under the Bush policy, according to the NIH.

Congress has passed bills to extend federal funding to research on the 200 or more cell lines that have been created with private money since the 2001 cutoff. The funding also would be made available for lines not yet developed; those are likely to come from thousands of leftover embryos being stored at fertility clinics.

Bush has vetoed the bills.

If Congress passes another such bill and the next president signs it, hundreds of cell lines could suddenly qualify for the stem-cell bank, Carlson said. That might force WiCell to scale up quickly, she said.

But owners of the newer lines, created with private money, might be less eager to contribute them to the federally-funded bank. The bank can’t compel owners of any cell lines to hand them over, Hei said.

Meanwhile, demand for some of the newer cells could be greater than that for the cells now in the bank because the newer cells were grown without using animal products. For cells in the bank, mouse feeder layers and cow serum were used as growth agents.

Some researchers say cells free of animal products are safer and more likely to be approved for use in human studies, though Hei said that’s not certain.

“Some people say you couldn’t use them (in human trials), but that’s flat-out wrong,” he said, because tests are showing they are safe.


To prepare for a possible influx of cells, WiCell workers are studying more efficient ways of freezing them.

They’ve also improved their shipping process. Until about a year ago, cells were transported to and from WiCell in Styrofoam boxes cooled by dry ice. But some cells started to thaw if the dry ice wasn’t replenished.

Now, “vapor shippers” – the mini-R2D2s, with thermoses lined with liquid nitrogen – are used. They can keep the cells frozen for about 18 days.

Such changes come as the stem cell bank world could soon become more populated.

The UK Stem Cell Bank outside of London is the only other government-funded bank for human embryonic stem cells. But Hei said there is talk of creating banks in Singapore, Massachusetts and California.

As the burgeoning stem-cell field begins to mature, Hei said a growing number of banks likely will specialize in different services.

But it’s hard to predict what will happen, he said, because politics continues to surround the research.

“In the long run, there will probably be a network of banks all around the world,” Hei said. “But it’s really difficult to plan long term in this field.”