Turning stem cells into therapies
Stem cells have the potential to treat a wide range of diseases, including diabetes, neurodegenerative diseases, spinal cord injury, and heart disease. Learn why these cells are such a powerful tool for treating disease as well as what the current hurdles are before new therapies can become available.
- How can stem cells treat disease?
- What diseases could be treated by stem cell research?
- How can I learn more about CIRM-funded research in a particular disease?
- Are there any stem cell-based therapies currently available?
- When will therapies based on embryonic stem cells become available?
- What about the therapies that are available oversears?
- Why does it take so long to create new therapies?
The most common way of thinking about stem cells treating disease is through a stem cell transplant. Embryonic stem cells are differentiated into the necessary cell type, then those mature cells replace tissue that is damaged by disease or injury. This type of treatment could be used to replace neurons damaged by spinal cord injury, stroke, Alzheimer’s disease, Parkinson’s disease, or other neurological problems. Cells grown to produce insulin could treat people with diabetes and heart muscle cells could repair damage after a heart attack. This list could conceivably include any tissue that is injured or diseased.
These are all exciting areas of research, but embryonic stem cell-based therapies go well beyond cell transplants. What researchers learn from studying how embryonic stem cells develop into heart muscle cells, for example, could provide clues about what factors may be able to directly induce the heart muscle to repair itself. The cells could be used to study disease, identify new drugs, or screen drugs for toxic side effects. Any of these would have a significant impact on human health without transplanting a single cell.
In theory, there’s no disease that is exempt from a possible treatment that comes out of stem cell research. Given that researchers may be able to study all cell types via embryonic stem cells, they have the potential to make breakthroughs in any disease.
CIRM has created disease pages for many of the major diseases being targeted by stem cell scientists. You can find those disease pages here.
You can also sort our complete list of CIRM awards to see what we've funded in different disease areas.
The first trials for embryonic stem cells have only just begun. Results from those won't be available for many years, once the necessary clinical trials are completed showing that the therapies are safe and that the work in treating disease. The only stem cell-based therapy currently in use is in bone marrow transplantation. Blood-forming stem cells in the bone marrow were the first stem cells to be identified and they are now the first to be used in the clinic.
The blood-forming stem cell is the component of bone marrow that is therapeutic in a bone marrow transplant. With the isolation of pure blood-forming stem cells it is now possible to transfer just the cells that are needed to replace the bone marrow. The cells migrate to appropriate bone marrow where they self-renew and rebuild the entire blood system.
Transplants of blood-forming stem cells have been used successfully in cancer treatments, and research suggests that they will be useful in treating autoimmune diseases and in helping people tolerate transplanted organs.
There are other therapies based on adult stem cells still in clinical trials. Until those trials are complete we won't know which stem cells are most effective in treating different diseases.
There is no way to predict when the first human embryonic stem cell therapies will become widely available. Applications are with the FDA to begin the first human trials of embryonic stem cell-based therapies, although only one of those trials has been approved. In general, the path from the first human trial to widespread use is on the order of a decade or two. That long time frame is a result of the many steps a therapy must go through in order to show that it is both safe and effective. Only once those steps are complete will the FDA approve the therapy for general use.
If embryonic stem cells follow a normal path it could still be many years before therapies based on embryonic stem cells are widely available. However, if researchers gave up on therapies that could take many years to develop we would not have any of the lifesaving medical technologies that are now commonplace such as recombinant insulin, bone marrow transplantation, or chemotherapy drugs.
Many overseas clinics advertise miraculous stem cell therapies for a wide range of incurable diseases. These clinics are referred to as stem cell tourism and are currently a source of concern for reputable stem cell scientists. The international clinics are proposing therapies that have not been tested for safety or even for effectiveness. In the past few years, patients who visited those clinics have died as a result of receiving unproven, untested stem cells.
The Internation Society for Stem Cell Research recently offered to help prospective patients review a clinic they are considering visiting. Scientists from the ISSCR will contact the clinic in question to find out what cells are being used by the clinic, and, at minimum, whether those cells have been tested for safety.
Learn more about the issue on our Stem Cell Tourism page.
Embryonic stem cells in a lab dish hold the potential to treat a wide range of diseases. However, the path from the lab to the clinic is a long one. Before testing those cells in a human disease, researchers must grow the right cell type, find a way to test those cells, and make sure the cells are safe in animals before moving to human trials.
A significant first hurdle in any embryonic stem cell-based therapy is coaxing cells that could be any cell type in the body into just the cell type that’s needed to treat a particular disease. The process of maturing the cells from their pluripotent state to an adult tissue type is called differentiation. This step is necessary because any therapy relies on implanting cells that are capable of replacing the lost tissue. In diabetes, for example, the implanted cells must be able to respond to blood sugar and produce insulin. In heart disease the implanted cells must be able to contract in unison with the existing heart muscle.
Guiding embryonic stem cells to be a particular cell type has been a major hurdle for stem cell researchers. Those cells normally develop within an embryo and receive a carefully choreographed series of signals from the surrounding tissue. In a lab dish, researchers have to mimic those signals in order to guide the cells down a developmental pathway. Add the signals in the wrong order or the wrong dose and the presumptive cardiac cells to treat heart disease may choose to remain immature or become another cell type instead.
Some of the signals needed to differentiate cells are known from the past hundred years of embryology research in frogs, mice, flies, and other organisms. Other signals are still unknown. Many CIRM-funded researchers are attempting to differentiate highly pure populations of mature cell types for therapies.
Once a researcher has a mature cell type in a lab dish, the next step is to find out whether those cells can function in the body. Embryonic stem cells that have matured into insulin-producing cells in a lab dish are only useful if they continue producing insulin inside a body. Likewise, researchers need to know that the cells can integrate into the surrounding tissue.
Testing the cells requires finding an animal model that mimics the human disease, then implanting the cells to see if they help treat the disease. These types of experiments can be painstaking. In the case of spinal cord injury, for example, the ultimate goal would be to find out whether the transplanted cells allow the injured animal full movement — the animal equivalent of a person being free from a wheelchair. However, even if the cells don’t return full movement, they may restore bladder function or other functions that would still be of enormous benefit to people. Researchers have to examine each of these possible outcomes.
In many cases testing the cells in a single animal model doesn’t provide enough information to know that the cells may be effective in humans. Most animal models of disease don’t perfectly mimic the human disease. For example, a mouse carrying the same mutation that causes cystic fibrosis in humans doesn’t have the same symptoms as people with the disease. A therapy based on embryonic stem cells that treats this mouse model of cystic fibrosis may not also work in humans. That’s why researchers often need to test the cells in many different animal models, in each case looking at all the possible outcomes.
The promise of embryonic stem cells is that they can form any type of cell in the body. The trouble is that when implanted into an animal they do just that, forming all tissue types in the form of tumors called teratomas. These tumors consist of a mass of many cells types and can include hair cells and many other tissues.
These teratomas are one reason why it is necessary to mature the embryonic stem cells into highly purified adult cell types before they are considered appropriate for implanting into humans. The mature cells are restricted to their one identity and don’t appear to revert to a teratoma-forming cell. Even when researchers have learned to mature cells into a single cell type, getting those cells pure enough to eliminate the risk of remaining immature cells forming teratomas has been extremely difficult.
UC Davis publication: UC Davis researcher focuses on stem cell safety
Transplanted stem cells, like any transplanted organ, can be recognized by the immune system as foreign and then rejected. In organ transplants such as liver, kidney, or heart, people must be on immune suppressive drugs for the rest of their lives to prevent the immune system from recognizing that organ as foreign and destroying it.
The likelihood of the immune system rejecting a transplant of embryonic stem cell-based tissue depends on the origin of that tissue. Stem cells isolated from IVF embryos will have a genetic makeup that will not match that of the person who receives the transplant. That person’s immune system will recognize those cells as foreign and reject the tissue unless a person is on powerful immune suppressive drugs.
Stem cells generated through SCNT or iPS cells would be a perfect genetic match for a person. The immune system would likely overlook that transplanted tissue, seeing it as a normal part of the body. Still, some researchers suggest that even if the cells are a perfect match they may not entirely escape the notice of the immune system. Cancer cells, for example, have the same genetic make up as surrounding tissue and yet the immune system will often identify and destroy early tumors. Until more information is available from animal studies it will be hard to know whether transplanted patient-specific cells are likely to call the attention of the immune system.
In order to be approved by the FDA for use in human trials, stem cells must be grown in what’s known as good manufacturing practice (GMP) conditions. Under GMP standards, a cell line has to be grown in such a way that each group of cells is grown in identical, repeatable conditions. This ensures that each batch of cells has the same properties, and each person getting a stem cell therapy would be getting an equivalent treatment. Although the FDA hasn’t issued guidelines for how pluripotent stem cells need to be grown in order to meet GMP standards, achieving this level of consistency could mean knowing the exact identity and quantity of every component in the media that the cells grow in.
Growing stem cells under strictly controlled conditions is still a challenge. Most pluripotent stem cells are grown on what’s known as feeder cells, which are a layer of animal or human cells on the lab dish that provide the nutrients the cells need to grow and divide. Those feeder cells produce a mix of factors that nourish the embryonic stem cells and allow those cells to thrive in the foreign environment of a lab dish. Scientists don’t currently know what it is exactly that the feeder cells provide, and so the use of those feeder cells probably won’t conform to GMP standards. CIRM is funding researchers who are trying to learn how to grow pluripotent stem cell lines in the absence of feeder cells, and to isolate new lines under GMP standards.