Researchers use stem cell research to perform 'human' drug testing in the body of mice.

Often in the course of drug trials, successful animal testing leads to failure at the level of human trials. However, two scientists at the Technion-Israel Institute of Technology may have created a method that could give an early indication whether or not a drug will be successful in human trials. By injecting human stem cells into lab animals, Karl Skorecki and Maty Tzukerman of the Technion-Israel Institute of Technology can perform “human” drug trials without using any human subjects.

By injecting human embryonic stem cells into the hind legs of lab mice, the researchers formed a teratoma—a growth consisting of human cartilage, blood vessels, fat tissue and connecting tissue. They then injected lab-grown cancer cells injected into the teratoma. The cancer cells proliferated and spread to the various tissues in the artificial human cellular environment. Thus the lab mice became a vehicle, or “sanctuary,” for testing anti-cancer drugs in human tissue, potentially giving a better assessment of how successful a drug could be if used in humans.

Skorecki, who is director of Technion’s Rappaport Family Institute for Research in the Medical Sciences, hopes that by using human stem cells in animals, researchers will cut down on the number of failed human drug trials, which cost researchers time, money and can sometimes cause health problems for human subjects.

In their research, Skorecki and Tzukerman, who served as lead author of the study, published in the April issue of Cancer Research, have already found one drug that is successful in destroying cancer in regular mice, but ineffective on mice with the human teratoma, leading them to believe the drug would fail human trials.

For some drugs, “the opposite might also be true,” said Skorecki. “There might be anti-cancer therapies, which have been prematurely rejected because they failed to eradicate a tumor when it was growing in a mouse, but might work in a human micro-environment formed in the teratoma.”

The unique use of stem cells could also serve as a buffer to protect humans against side effects or overdosing from drugs, something that would be difficult to predict from testing in traditional lab mice.

“Because we have human tissue right there in the mouse we might see toxicity to human tissue,” said Skorecki, “which we may like to know about before administering a drug to a human being.”

Since the teratoma contains the entire “panoply of human cell types in a semi-organized fashion,” a range of drugs designed to treat cancer and other diseases can be tested on these chimeras, said Skorecki.

The research team’s next goal is to combine the basic research they performed at the Technion-Israel Institute with the resources of a private pharmaceutical company to begin large scale “human” drug testing within the bodies of lab mice.

While stem cell use is limited in the United States, the innovative method of ‘human’ drug testing, which is patented by the Technion Institute, provides an alternative field of research for what is still a controversial area of science. 

“There are many uses of human embryonic stem cells as an experimental platform without ever injecting them into a human being,” sad Skorecki. “This is just one example.”

Although the alternative method of research does not avoid harvesting embryos to create stem cells—the action at the heart of the moral debate against stem cell research—Skorecki believes that this type of research will become more commonplace and could pave the way for other controversial research with stem cells.

“Long before embryonic stem cells are going to be used in clinical regenerative medicine, which is where all of the hope and some of the hype is, I think there is an opportunity to use embryonic stem cells for drug testing,” he said.

Originally published April 27, 2006

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