EXCITEMENT about the potential of stem cells for curing all manner of ills is being tempered by two new studies that highlight the potential dangers. They show that even stem cells taken from adults can turn cancerous if they are allowed to multiply for too long outside the body.
Researchers have long known that there is a cancer risk with stem cells extracted from very early embryos. Until they change into more specialised tissue, they can form aggressive cancers called teratomas when injected into animals.
Until now, it has been widely assumed that adult stem cells, such as those taken from bone marrow, do not form cancers. But the latest studies suggest that adult stem cells are safe only if the number of times they are allowed to divide outside the body is limited.
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A team at the Autonomous University of Madrid in Spain grew human mesenchymal stem cells extracted from fat tissue for up to eight months. During this time the cells divided between 90 and 140 times. When transplanted into animals, the oldest cells formed cancers (Cancer Research, vol 65, p 3035).
The pioneering treatments with bone-marrow stem cells that are already being tested in people, for instance for treating damaged hearts, should be safe because the cells are only briefly grown outside the body. 鈥淚n normal conditions in clinical applications we think the cells are pretty safe, but we must be careful,鈥 says Antonio Bernad, head of the Madrid team. 鈥淭he key is not to grow them for too long.鈥 However, treatments that rely on multiplying a small number of stem cells through many generations, or on cell lines maintained for years in the stem cell banks currently being established around the world, may not be safe.
Stem cells grown in culture for a long time probably become cancerous because they start making telomerase, an enzyme that immortalises cells by rejuvenating the 鈥渇use鈥 on chromosomes that normally limits the number of times cells can divide. A Danish team whose results appear in the same issue (p 3126) found that permanently switching on the telomerase gene in mesenchymal stem cells eventually turns them cancerous.
鈥淐ell lines maintained for years in the stem cell banks being established around the world may not be safe鈥
鈥淎lthough it鈥檚 an artificial situation, it鈥檚 clearly sufficient for them to acquire the ability to become tumorigenic,鈥 says Jorge Burns, head of the team at the University Hospital of Odense.
Until the cells start making telomerase, they should be safe. The Madrid team suggests around 60 generations as a provisional cut-off point, but more research needs to be done to establish a safe limit. 鈥淲e need to know where to draw the line between safe and unsafe expansion of cells even in non-telomerase-producing cells,鈥 Burns says.
鈥淏oth these papers reinforce the potential danger of using stem cells,鈥 says Robert Lanza of Advanced Cell Technology, a stem cell company in Worcester, Massachusetts. 鈥淭hey underscore the need for extensive safety testing before any type of stem cell is used for medical therapy.鈥
