M. William Lensch, PhD
M. William Lensch, PhD, instructor in pediatrics, Harvard Medical School and senior scientist, George Q. Daley Laboratory, Boston, Massachusetts.
Wouldn’t it be great if there was a way to get the genetic power of embryonic stem cells from sources other than embryos? Scientists are looking at possible solutions to that dilemma, since embryonic stem cells are among the most promising avenues to treatment or cure for a variety of serious diseases, but their use comes with lots of ethical baggage. Having read some really exciting developments cited in journals and research papers, I called M. William Lensch, PhD, an instructor in pediatrics at Harvard Medical School and senior scientist at the George Q. Daley Laboratory at Children’s Hospital in Boston, to get his perspective on what looks new and promising. He agreed there’s much to be enthusiastic about, including research pointing to new ways to study, and someday treat, disease.
But let’s start out with an overview on the topic, because it is a complicated one.
Think of your body as a working cell factory, the kind with numerous departments, each making parts on demand. These departments have limits, however. Break a leg and the bone cell department is at your service making cells to heal the damage, but it can’t send over the right kind of cells to cure your type I diabetes.
Some stem cells, however, have the capacity to “morph” into other types of cells. Some are especially flexible, able to work in several different but related departments. For instance, hematopoietic (blood) stem cells can give rise to any kind of blood cell. Other stem cells can make a broader range of cell types — bone marrow stromal stem cells are able to produce bone, fat, cartilage and fibrous connective tissue cells. But neither of these types can grow brain cells or heart cells — it’s just not their department. Then there’s the “pluripotent” cell… this type of stem cell has the capacity to develop into almost every cell type and therefore has incredible potential for clinical treatments. The problem is these cells are typically derived — with their donors’ permission — from eggs fertilized in vitro, which would otherwise have been discarded by fertility clinics.
Another challenge lies in creating stem cells that patients’ bodies won’t reject as foreign, Dr. Lensch explained. Such rejection from a donor’s stem cells can result in treatment failure and even in death. Some kinds of stem cells may also carry the risk of tumor formation in certain situations. And many serious diseases involve multiple types of cells and therefore would require a variety of transplanted ones for treatment. These are among the difficult challenges scientists in the field are grappling with.
Recently scientists around the world, including in the United States, were able to coax mature cells (non-stem cells) sourced from skin biopsies into behaving like embryonic stem cells. These are called “induced pluripotent stem cells” or iPS cells. Their ability to give rise to all cell types is still being studied, but shows definite promise. Research continues on whether iPS cells are close enough to embryonic stem cells to make them an effective — and, to some, more ethical — alternative.
One application of the iPS cells is well under way. Harvard University stem cell researchers, including George Q. Daley, MD, PhD, have developed lines of disease-specific stem cells from induced pluripotent cells made from cells donated by individuals, each suffering from one of 10 specific diseases, including type I diabetes, Downs Syndrome, Huntington disease and two different forms of muscular dystrophy. These will ultimately be used as a testing ground for treatments, so experiments won’t have to be done with real-life patients. Researchers acknowledge that treatments based on this work are still many years away, but are excited about the opportunities such cell lines may provide, enabling them to study the origins and development of these illnesses.
Important advancements are also being made in tissue engineering with stem cells. Researchers in Spain recently announced that they had successfully engineered a human windpipe in a laboratory, using a donated trachea with stem cells harvested from a 30-year-old woman whose trachea had been damaged by tuberculosis. Once engineered, the healthy new trachea was implanted as a replacement for the patient’s diseased one. Four months after the transplant, her doctors reported that she was able to climb stairs, care for her children and even go dancing. In addition to having received an organ transplant created with her own stem cells, she also was able to forgo the powerful drugs (which have their own dangerous side effects) usually required to prevent rejection of the transplant.
Because many people find the use of embryonic stem cells ethically troublesome, the search for new sources of stem cells is always on. To date, researchers have isolated multiple varieties of stem cells from many different sources, including umbilical cord blood and the placenta (both normally discarded after childbirth), the pulp from inside baby teeth and wisdom teeth, menstrual blood, testicular tissue, amniotic fluid, and cells found in hair follicles. Work continues on the efficacy of each of these sources at generating stem cells for medical purposes.
Dr. Lensch told me that in his view, it’s overly optimistic to believe that these cells can give rise to the same range of cells that embryonic stem cells or iPS cells can. “The truth is that they simply are not as potent and effective at making multiple types of tissues as embryonic stem cells,” he said, noting that “they’re very interesting in their own right, and may have a lot to teach us.” For instance, he said, adult stem cells from bone marrow have been used to effectively treat certain blood diseases since the mid 1980s, and more currently blood stem cells from umbilical cord tissue have provided effective treatment for some diseases, especially in children, including leukemia and certain genetic disorders of bone marrow or metabolism. Dr. Lensch notes that those treatments have worked because the problem is biologically simple — only a single type of cell needs to be fixed. “To repair damage from something like a stroke, though, is far more difficult since the damage involves so many different kinds of interrelated neural cells,” he explains. “We’re not there yet.”
Dr. Lensch says this is why this field is so exciting, though. “Every new discovery, everything we learn, puts us closer to something else that may be of real benefit. Even when we fail, we go back to find out why. When people get upset because we haven’t yet fulfilled the promise of stem cells, I tell them to think of treatments like organ transplants. We tried over and over again to make transplants work, and we failed repeatedly. And then one day, we succeeded.”