Scientists are discovering new treatments with stem cells time

In utero stem-cell transplants had been tried before for the blood disorder but with limited success. Blood stem cells, which develop into all of the different types of blood cells, are extracted from a donor’s bone marrow, processed in a lab and injected directly into the umbilical vein connecting the fetus to the mother’s placenta. Ideally, the donor’s healthy stem cells then start dividing and take over for the fetus’ defective blood cells. But removing bone marrow can be risky in pregnant women, so past trials involving alpha thalassemia used stem cells from fathers, which were often rejected. This new trial challenged the ethical question: Was it worth the risk to the mother in order to possibly save the fetus? There was also a chance the transplant could harm Obar’s daughter more than it helped.

But on the basis of new studies suggesting that a developing fetus would tolerate a mother’s transplanted cells better than a father’s, Dr. Tippi Mackenzie, a professor of surgery at UCSF and the leader of the study, believed it was worth a shot.

With stem cells like those found in bone marrow, scientists are taking advantage of what the body does naturally: generate itself anew. Many of the adult body’s organs and tissues, including fat cells and blood, are equipped with their own stash of stem cells whose sole job is to regenerate cells and tissues when older ones are damaged or die off and which can be harvested for research and growth outside the body.

Some organs are not endowed with these large stem-cell reservoirs, however, most notably the brain and heart muscle. So more than two decades ago, scientists found another source of these flexible cells–in embryos that were donated for research from in vitro fertilization clinics. They learned how to grow these cells in the lab into any cells in the body. That opened the possibility that conditions like heart disease, diabetes or even psychiatric disorders might eventually be treated by replacing damaged tissues or organs with healthy ones, which could provide cures and treatments that didn’t require drugs or surgery.

In the quest to try these treatments on patients, there have been false starts. In 2009, the FDA approved the first embryonic-stem-cell clinical trial, which involved transplanting nerve cells made from stem cells into paralyzed people to restore the function of spinal nerves. In initial tests with mice, however, the transplanted cells started to form concerning clumps, which were not tumors but raised enough alarms about the safety of the therapy that the FDA put the study on hold; after resuming the trial, the company conducting the research eventually decided to stop it.

Now, with more years of study and experience, scientists are preparing to test whether stem cells that transform into heart muscle could replace dead tissue after a heart attack, for example, or whether pancreatic cells that can’t produce enough insulin might be replaced with new cells that can do the job in people with Type 1 diabetes. Researchers even hope to one day treat brain disorders like Parkinson’s with new neurons made from stem cells that can replace the damaged motor nerves in the brain that lead to uncontrollable tremors.

So far, the mini-brains contain the same 20,000 genes that any human cell’s DNA contains and produce all of the relevant proteins that any brain cell would. (Because they lack all the structures of a whole brain, however, Markx and de Jong prefer to call them “organoids.”) The balls of brain tissue he is nurturing came from iPS cells generated from people in the Amish community. Some are from healthy people, others from those affected by a rare genetic brain disorder that involves autism-spectrum symptoms, intellectual disability and epileptic seizures. The stem cells were developed into the brain organoids to study how that genetic aberration affects normal brain development. “Now we have this opportunity to study the processes of how [brain cells] grow and develop and observe them in the lab,” de Jong says. He and his team are investigating how closely the organoids replicate actual disease processes in people and are hoping to eventually use the mini-brain cells to screen for promising drugs that may undo the effects of the mutation.

Such stem-cell-based biotech companies are popping up throughout the country to address different types of diseases. At Semma Therapeutics, based in Cambridge, Mass., Douglas Melton, a co-director of the Harvard Stem Cell Institute, is pursuing ways to generate a population of insulin-pumping pancreatic cells from people affected by Type 1 diabetes, like his two children. His latest studies showed that the cells, made from iPS cells, can detect and respond to changing levels of sugar and effectively dial up and down how much insulin they produce. But with Type 1 diabetes, replacing these cells with new ones from stem cells doesn’t solve the entire problem, since the immune system seems to be attacking the pancreatic cells. So he and his colleagues at Semma developed a way to protect the newly formed insulin-making pancreatic cells from destruction by encasing them in a membrane that can slip past the immune system. Melton hopes to test that delivery system, and his insulin-making cells made from stem cells, in the next two years. “Insulin was discovered in 1920, and I like the idea that at the 100-year mark we may be done injecting insulin,” he says.