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Renaissance cells
Stem cells build tissue, fight tumors
By Bijal P. Trivedi

Preliminary studies showing that brain cancers in mice can be reduced by 80 percent using a novel method of drug delivery were presented by Evan Snyder of Children's Hospital, in Boston, at the third annual meeting of the American Society of Gene Therapy. Snyder also reported work showing that neural stem cells are able to "sense" brain injuries, migrate toward damaged areas and repopulate the regions with healthy brain tissue. The work could have broad implications for stroke and cancer patients, but clinical trials are at least one year away.

The ability to migrate to specific targets is what makes the cells particularly well suited to delivering therapeutic chemicals or genes, according to Snyder.

A string of migratory stem cells (small arrow) seeks out damaged brain tissue (large arrow).

In a series of studies done in mice, the Boston researchers implanted drug-bearing neural stem cells on the opposite side of the brain to the tumor and were able to watch the stem cells, which were identified by tagging them with a blue dye, migrate toward and infiltrate the tumor. The stem cells carry a gene for cytosine deaminase that works in concert with 5-fluorocytosine to kill replicating tumor cells without damaging normal healthy tissue. The tumors shrunk by an average of 80 percent.

"As long as the stem cells carrying the genes do not divide, they shouldn't be destroyed. Ideally, the stem cells would just go into the tumor, destroy it, and differentiate to replace the cancer with healthy cells," says Snyder.

One rather dramatic slide, presented at the meeting, shows one of the stem cells "pursuing" a tumor cell that had spread beyond the primary site. It is as if the stem cell is "chasing the bad guys out of town," says Snyder. The ability of the stem cells to "hunt down" the tumor cells could be particularly important in treating gliomas that can spread from one side of the brain to the other.

"Snyder's work is intriguing and very exciting, but whether this treatment will work in larger animals, like humans, still remains to be seen," says Beverly Davidson, of the University of Iowa, who moderated the meeting session at which Snyder spoke.

In addition to the brain cancer studies, Snyder showed how unaltered neural stem cells could find regions of the brain where cells died after blood and oxygen were cut off.

Stem cells (small arrow) colonize a damaged area of the brain filling it with new tissue (large arrow).

In one mouse, stem cells were transplanted on one side of the brain and seven days later, tissue damage was induced in a small region on the opposite side. Later analysis showed that the stem cells had migrated toward the damaged area. A different experiment showed that when the stem cells are implanted directly into the damaged region the stem cells divided and repopulated the area with a range of healthy brain cells: neurons, astrocytes and oligodendrocytes. "This therapy is the equivalent of a bone marrow transplant, but for the brain," says Snyder.

But simply reestablishing cell populations in injured regions of the brain does not mean that neural networks will be reestablished, says Davidson.

What we need to show is that repopulating a damaged area with a range of stem cell derived brain cells actually restores some lost brain functions. "Nailing down this cause and effect here will be quite a challenge," says Snyder.

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