A decade ago, the Yale Stem Cell Center launched amidst a wave of optimism about the ability of these cells to transform medicine. Researchers made a somewhat controversial decision to focus on understanding the basic science and inner workings of stem cells—rather than developing therapies for specific diseases.
Ten years later, this strategy is paying dividends.
Many advances achieved by Yale scientists are quickly approaching clinical relevance. Progress came even faster than expected. “We started by exploring the mechanisms of stem cells and that enabled us to use rational design for experiments and therapies,” says Haifan Lin, PhD, the center’s founding director. “Our research is no longer led by a trial-and-error approach.
As scientists better understand stem cells, which are located throughout the human body, they’re able to grow them more efficiently into a desired cell type. These cells could then, theoretically, be used to create new organs or to treat diseases in novel ways. In essence, stem cells promise to cure ailments, rather than address the symptoms, as most current medications do today.
A cure for congenital heart defects and more
In 2009, Yale became the first Food and Drug Administration-approved site in the country to implant artificially made heart vessels grown from a patient’s cells back into the patient. This procedure can cure congenital heart defects, a condition that affects nearly 1 percent of U.S. newborns. Now, in clinical trials, Yale scientists and physicians are using stem cells to treat stroke and spinal cord injury patients. They are also using stem cells to grow new blood vessels in petri dishes and using stem cell-grown tissue to find new cardiovascular drugs. In the next decade, they may use insights from ongoing research to more effectively combat cancer.
Indeed, stem cell research across the country and the world is beginning to deliver on its promise. Stem cell treatments have become more commonplace, with reports of patients with everything from brain injuries to multiple sclerosis showing fewer symptoms after receiving intravenous infusions of the cells.
At Yale, basic research has allowed researchers to collect stem cells from anywhere in the patient’s body—from skin, fat tissue, or bone marrow,/ for example—and reprogram them into necessary cell types in the body. For instance, Yale neurology scientists Jeffery Kocsis, PhD, and Stephen Waxman, MD, PhD, are experimenting with stem cell therapies for stroke victims. They have isolated and purified stem cells from patients’ bone marrow and inserted them back into the body through intravenous injections—with encouraging results coming from a collaborative clinical trial at Sapporo Medical University in Japan.
New hope for treating stroke and spinal cord injury
Kocsis and Waxman have found that infusions of mesenchymal stem cells release molecules into the body that encourage the repair of neurons and blood vessels damaged during strokes. They believe that if patients receive stem cell treatments rather than blood-thinning medication alone, they may achieve significant recovery.
The pair of researchers hopes to achieve similar results in clinical trials—also in Japan—for patients with spinal cord injuries. Kocsis has observed noticeable improvements in the early stages of the trials. “Some patients have moved two to three grades (on a muscle movement scale) in a positive direction,” he says.
In another research area, Yale scientists have made progress toward engineering new blood vessels—even as organs grown from stem cells remain out of reach. For patients with chronic conditions such as cardiovascular disease or diabetes, current medications work by maintaining, not repairing, blood vessels. The hope is that someday patients might be able receive new blood vessels created from their own stem cells. Earlier this year, a research team headed by biomedical engineer Laura Niklason, MD, PhD, successfully implanted a vessel grown using only human stem cells into a rat. “Right now the vessels we grow are about one-third as strong as they need to be,” Niklason says. Researchers in her lab and others on the Yale campus are investigating how to use stem cells to create more collagen, a protein which helps gives blood vessels their sturdy structure.
Using stem cells for personalized medicine
Yale researchers also intend to aid pharmaceutical companies in finding new treatments for cardiovascular patients. Using a patient’s own stem cells, a research team led by stem cell scientist Yibing Qyang, PhD, created a vascular ring, a piece of a living blood vessel, in a lab dish. The goal is to produce a replica of a human blood vessel, in order to test the effectiveness of potential cardiovascular drugs. The vascular ring could also be used in personalized medicine to observe how an individual will respond to a particular drug before administering it.
Yale Stem Cell Center Director Lin has focused much of his own research on understanding how certain molecules in the body interact with stem cells. Eighteen years ago, Lin discovered a class of genes linked to human fertility. More recently, his lab discovered that these genes become overly active in many types of cancers. This led Lin to wonder: If he created a molecule that could reduce these genes’ activity in cancer cells, would he be able to stop the growth of cancer cells? The answer turned out to be—yes.
Lin recalls a eureka moment earlier this year when his team treated aggressively dividing breast cancer cells with a molecule that suppressed the activity of these specific genes. Immediately the cancer cell division slowed. “It appears that when these genes become hyperactive in breast cells, it causes regular breast cells to become cancer cells,” Lin says. “This may be true for other types of cancers.” Now, Lin and lab scientists are working to modify the molecule so it can be used in human patients to treat cancers. This could lead to a drug that would target only cancer cells, because normal body cells—with the exception of sperm and egg cells—do not express these genes. “Basically this could be a whole new pathway for cancer drug discovery,” Lin says.
In the center’s next 10 years, Lin hopes that researchers will be able to break new ground in stem cell research, including in stem cell genetics, thanks in part to improved DNA sequencing technology. Powerful computers and analytics tools will help scientists to better understand how genes work and how their activities vary in different patients.
Niklason shares Lin’s optimism. “We are still very early in the game,” she says. “But I think things are taking off.”