Is life possible without water? Work by scientists to resuscitate mammalian cells subjected to freezing or drying suggests it may be. In one remarkable experiment, cells were revived after desiccation for 5 days following treatment with trehalose, a simple sugar molecule that allows certain forms of life to exist entirely without water. The work suggests that trehalose will be an extremely useful additive for protecting mammalian cells during drying or cryopreservation, with implications for cell and tissue storage and transportation in basic research and biomedicine.

   Some organisms astound us with their abilities to survive, even thrive, in the most extreme and unlikely conditions. Trehalose was originally identified as a life-preserving molecule in organisms such as baker's yeast and tardigrades -- bizarre microscopic bugs that can lie dormant in a mummified state for decades without any water. These organisms naturally synthesize trehalose, which preserves the structural integrity of cells, allowing them to revive and fully function when conditions become more hospitable.

   Previous work had suggested that trehalose is of use for revitalizing frozen cells. For researchers aiming to use trehalose to protect mammalian cells, the big problem is how to get the molecule to penetrate cell membranes. In this issue, two new papers describe different approaches for incorporating trehalose into human cells. In the first approach, Fred Levine and colleagues have infected human cells with an adenovirus containing two genes encoding the enzymes for synthesizing trehalose. After thorough dehydration -- to the point at which no water was detectable -- the modified cells were consistently able to be resurrected after three days, and in some cases up to five days following desiccation. In the same study, trehalose was shown to have negligible toxic effects on mammalian cells. In a different approach, Mehmet Toner and colleagues have achieved similar results when reviving human cells following freezing. They used an engineered bacterial protein to ferry trehalose through the cell membrane and into cells. When these cells were frozen 72% survived, compared with only 0.4% survival for cells that didn't receive trehalose.

Authors:

Dr. Mehmet Toner
Shriners Hospital of Children
51 Blossom Street
Boston, MA 02114
Tel: 617 371 4876
Fax: 617 371 4950
mtoner@sbi.org

Fred Levine
University of California, San Diego
Center for Molecular Genetics
La Jolla, CA 92093-0634
Tel: (858) 534-5979
Fax: 858-534-1422
flevine@ucsd.edu