Stem cells captured the public imagination a long time ago. Patients and researchers believe that stem cells could be the key to regenerative medicine. However, studies haven’t kept up with the potential. Stem cells are still far more therapeutic in theory than in practice.
Researchers are now excited about the potential drug discovery application of stem cells. Around eight years ago pharmaceutical companies began seriously looking into using stem cells to test their products.
Animal studies are rife with moral problems and don’t tell scientists how a drug will truly react with the human body. A drug can produce a strong, reliable effect in animals without producing the same effect in human beings.
Stem cells can be used to test the toxicity of the new drugs as well as inform their development.
“I believe the biggest impact to date of induced pluripotent stem cell technology is not regenerative medicine, but in making disease models, drug discovery, and toxicology testing,” Nobel Prize-winning stem cell researcher Shinya Yamanaka said.
Why Stem Cells?
Stem cells are attractive in drug research for a variety of reasons. Drugs can have fantastic results in animal studies and fail miserably when it comes time for human trials. Stem cells are far more relevant because they’re actual human tissue.
Scientists can use stem cells to study how disease develops in the human body. Pluripotent adult stem cells are taken from the patient’s own body. Scientists can grow diseased petri dish cells that are genetically identical to the patient. The cells can then be studied as the disease progresses.
Using Stem Cells to Test for Toxicity
Animals are closely related to us but their bodies are different. Drugs that are toxic to animals can be safe for humans and vice versa. Animal testing, therefore, is far from an exact science. Researchers have to spend a lot of time chasing down ends.
Multiple companies are creating stem cells for scientists to use in lieu of animals. In 2012, a study exposed cardiac stem cells to known toxins. The cells had the predicted reactions. Biotech company Genentech believes that their human stem cells can not only replace animals in drug testing but outperform them.
“Many of the animal models out there are poor, demonstrating great efficacy in the mouse, but not repeating in man during late-stage clinical trials. Therefore having an in vitro model years before, which can actually recapitulate human disease, would be a huge advantage,” senior director for strategic and corporate development at iPierian, a biopharmaceutical company, Adam Rosenthal explained.
When the heart stem cells were exposed to compounds that hadn’t been identified as toxic until they were already on the market, they were damaged. If these cells had been used during the initial testing phase, the drugs never would have made it to the market.
“These are compounds which went all the way through animal testing, then went through phase I, II, III and then were licensed in many cases by the FDA,” the study author said.
In addition to the obvious health benefits, using stem cells to weed out drugs with dangerous side effects before they reach the market could save the industry millions of dollars in wasted development costs. They could also be valuable tools for the discovery of new drugs, an application for which both Cellular Dynamics and GE Healthcare market their cells.
Stem Cells in Disease Modeling
There are available stem cell models for a host of diseases. They were extracted from patients in 2010. These cells can be used model how disease affects human organs. In 2013, scientists built a stem cell organoid that resembled a young human brain. It was an exciting first step.
The research is just beginning.
Scientists can also use patient’s own person cells for treatment. The patient’s care can be fine-tuned this way. If that’s not an option, researchers can use multiple diverse stem cell lines to create a personalized treatment plan.
Three years ago, a company announced progress with an anti-epileptic drug. The patients’ brain cells were analyzed to predict the drug’s usefulness for their case.
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The research is still in its infancy, although it shows a lot of promise. There are other drawbacks. Heart stem cells, for instance, can be used to predict how the heart will react to drugs, not how the body as a whole will react. Researchers aren’t quite ready to replace animals yet.
There are still many things that researchers don’t know.
“What human ES cells and iPS cells now do is give you access to the basic building blocks of the human body, just for basic study,” said James Thomson, director of regenerative biology at the Morgridge Institute for Research.
“We will understand the human body at a much greater detail because of these cells. Exactly how the cells will be used are not clear… But I do think it will profoundly change human medicine.”
Both the public and the academic community are intensely interested in stem cells. There are a huge number of studies every year. Although researchers at first believed that the main value of stem cells was in their regenerative potential, many now think that their biggest purpose will be in drug development.
If scientists had an accurate and reliable way to test for drug toxicity, it would be a boon for patients and physicians. Right now, it takes a very long time for drugs to be approved by the Food and Drug Administration and introduced to the public. The agency is understandably wary about unvetted drugs. Using stem cells instead of animals would greatly speed up this process.
Scientists are examining all the potential uses of stem cells.
One problem with the fact that stem cells don’t offer a full body response was noted by Massachusetts Institute of Technology chemistry and toxicology professor Steven Tannenbaum.
“More than 90 percent of drugs are metabolized in the liver to other forms of the drug, some of which might be toxic,” he said. “This group has taken valproic acid, which is normally extensively metabolized in the body, and exposed it under unrealistic conditions.”
Tannenbaum was referencing a study that looked at the effects of valproic acid on embryonic stem cells.
There are challenges to the research but there’s no reason to believe that they can’t be overcome. For instance, some of the stem cells could be coaxed into becoming liver cells.
“As long as we can make the cells from human embryonic stem cells, then once we have the mature cells in a dish, we could discover biomarkers in liver toxicity,” the valproic acid study’s lead author said.
“It’s a very versatile platform.”
Although the research is exciting, it’s going to be a while before stem cell treatments are readily accessible to the public. It will also be a while before stem cells completely replace animals in drug testing, assuming that it’s going to happen at all.
A breakthrough could happen any day. The research is ongoing and heavily funded. At the moment, patients have access to stem cell clinics and experimental treatments.