Center works to bring life to that which is ?dead?
Blood banks show interest
The No. 1 clinical problem with transfusion of platelets from blood banks is septic shock, caused by bacterial contamination, Tablin said. It's a particular problem for U.S. armed forces because the three- to five-day shelf life for platelets is too short to ship them to combat areas. "The only way they can get platelets is in direct, whole-blood transfusions that are done literally on the spot."
While blood banks refrigerate and store red blood cells up to 42 days, freeze-drying could further extend their shelf life, increase supplies and make them more portable. That would make donated red blood more available in developing countries where there is little refrigeration, as well as in battle zones.
"We hope that one day every soldier will be able to carry his own freeze-dried red blood cells with him on the battlefield," said Nellie Tsvetkova, who leads the red blood cell research team. Tsvetkova is a Bulgarian native who did her doctoral research on cell membranes at a Sofia cryobiology institute where other scientists developed food and bandages for the Russian cosmonauts.
A challenge in freeze-drying red blood cells, she said, is preserving their hemoglobin, which carries oxygen to all the tissues in the body and removes carbon dioxide.
But the addition of trehalose shows promise here, too.
Preserving stem cells and other nucleated cells presents harder challenges still because the nuclei, which hold the cells' DNA, must survive intact in order for the cells to divide and grow after they are revived.
Ann Oliver, who directs the center's nucleated-cell research, envisions a day when bone-marrow stem cells might be used to form new bone or other tissue.
In addition to trehalose, Oliver and her team are studying the cell-protecting qualities of heat-shock proteins from brine shrimp and arbutin, a substance that is found in resurrection plants and used in skin-lightening cosmetics. "Our goal is to create a dehydrated product that after hydration grows viable cells," Oliver said.
A new wave of therapies
Other researchers in the field say such work is critical to a new wave of medicine made from cells.
"There's no question that in the next 10 to 20 years we will be using cells for therapeutic reasons," said Mehmet Toner, professor of biomedical engineering at Harvard Medical School and Massachusetts General Hospital. "They are more complicated drugs in some ways. The preservation and stabilization of mammalian cells has become a much more important problem in medicine as these applications become reality."
Crowe is a world leader in cryopreservation, Toner said. "What he really has done, in my opinion, is create a whole new field." His critical and creative work, joined with Tablin's expertise, has made the latest advances possible, he added.
A method patented by the Crowes in 1989 for freeze-drying liposomes, cell-like sacs made from fatty substances used in medicines and cosmetics, is already used to preserve a drug for treating a deadly systemic fungal infection that afflicts AIDS and other immune-depressed patients. "The physician gets a serum bottle with dried liposomes at the bottom," Crowe said. "He squirts in water, shakes it up, and they're ready to go. It's just that simple."
They are also working on ways to freeze-dry and store a new drug the company is developing to treat cancer patients.
The Crowes and Tablin say such unexpected benefits show the importance of basic, curiosity-driven science. "There was no thought of any practical purpose to this," said Lois Crowe, who is now retired. "That was just an offshoot. The experiments were really done to prove a principle: that trehalose and some other sugars could preserve (cell) membranes."
John Crowe said curiosity still drives the research at the center. "At a fundamental level, we don't understand all the mechanisms. We feel that we have to understand how it works."
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