GENETIC engineering can keep adult stem cells alive long enough to repair damaged hearts. But it is not yet clear how the approach could be turned into a practical treatment for the millions who suffer heart attacks each year.
A few small trials on humans have already shown that injecting adult stem cells into the bloodstream after a bypass operation can produce some improvements in heart function (快猫短视频, 11 January, p 14). But most of the cells die before they can do any good. Several animal experiments, says Victor Dzau of Harvard Medical School, have found that virtually all the stem cells die within four days.
Now his team has shown that modifying stem cells before injecting them back into the body might solve the problem. Dzau used a virus to insert a gene called Akt1 into rat stem cells derived from bone marrow. The extra Akt protein produced blocks the signals that trigger cell suicide.
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The engineered cells were injected into rats with damaged hearts. Two weeks later, the rats鈥� hearts functioned as well as normal (Nature Medicine, DOI: 10.1038/nm912). The team thinks the modification allowed the stem cells to survive long enough to turn into heart muscle cells, replacing damaged tissue.
The results are 鈥減retty darn dramatic鈥�, says Charles Murry of the University of Washington in Seattle. The method could spell the end of the cell-death problem that has limited the effectiveness of stem cell therapies, he says.
However, time is of the essence when treating heart attacks. It already takes about a day to extract and purify bone-marrow stem cells. This cannot be done in advance because to avoid immune rejection, each individual patient has to be treated with their own stem cells. Adding a genetic engineering step like Dzau鈥檚 would take even longer, probably at least a week.
Dzau says it should soon be feasible to extract and maintain personal stem cell stocks for patients at particularly high risk of heart disease, but few could afford this. An alternative is to create a bank of many different stem cell lines, from which immunologically matched cells could be found for anyone.
But this might turn out to be unnecessary: a few studies have hinted that the bone-marrow stem cells used by Dzau鈥檚 group do not trigger rejection (快猫短视频, 15 December 2001, p 4). If so, doctors could use cells from any donor to treat any individual.
There is a possibility that blocking cell-suicide signals will increase the chances of the stem cells becoming cancerous. But Dzau thinks the risk is low. Heart muscle cells divide only rarely, if ever, he says, so once the Akt1-modified cells turn into heart muscle cells there is little danger.
Murry, however, thinks the team has yet to prove that the engineered cells confer their benefits by turning into heart muscle cells. He points out that there are other ways in which stem cells can improve function. For instance, it was recently reported that stem cells restored limb movement in rats with spinal cord injuries, but rather than becoming new nerve cells, the stem cells produced chemicals that enhanced the function of existing cells.