The Promise of Stem Cells
Studying stem cells will help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.
Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis.
Have human embryonic stem cells successfully treated any human diseases?
Scientists have been able to do experiments with human embryonic stem cells (hESC) only since 1998, when a group led by Dr. James Thomson at the University of Wisconsin developed a technique to isolate and grow the cells. Although hESCs are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its early stages.
The NIH funded its first basic research study on hESCs in 2002. Since that time, biotechnology companies have built upon those basic foundations to begin developing stem cell-based human therapies. There are currently three clinical trials using cells derived from human embryonic stem cells:
Geron, a biotechnology company located in Menlo Park, California is currently enrolling patients for its clinical trial of a hESC-derived therapy. The trial is testing the safety of using hESC-derived cells to achieve restoration of spinal cord function. Oligodendrocyte progenitor cells derived from hESCs are injected directly into the lesion site of the patient’s injured spinal cord. Geron announced that the first patient was treated in Atlanta in October 2010, and a second patient was enrolled and treated in Chicago in May 2011.
ACT is a biotechnology company with laboratories in Marlborough, Massachusetts and corporate offices in Santa Monica, California. ACT has begun enrolling patients for Phase I (safety and tolerability) clinical trials of two hESC-derived stem cell products:
The second ACT trial is testing the safety of hESC-derived retinal cells to treat patients with age-related macular degeneration. On July 14, 2011, ACT announced that doctors at UCLA had treated one patient in each of its clinical trials.
What about Other Types of Stem Cells?
Bone marrow contains blood-forming stem cells (hematopoietic stem cells) that have been used for decades to treat blood cancers and other blood disorders. Umbilical cord blood is another source of hematopoietic stem cells that is being used in treatment. You can see a list of diseases that may currently be treated with hematopoietic stem cells at the website of the National Marrow Donor Program.
Participating in Clinical Trials
Scientists are testing the abilities of many different types of stem cells to treat certain diseases. You can search for clinical trials using stem cells (or other methods) to treat a specific disease at ClinicalTrials.gov.
Search source: http://stemcells.nih.gov/info/health.asp
Benefits of Stem Cells
With all the controversy surrounding stem cells you may have missed hearing about many of the benefits for the health and medical fields. You may not even be aware that stem cells already have many applications for treating disease. Their potential to treat even more diseases in the future means that scientists are working hard to learn about how stem cells function and how they can treat some of the more serious diseases affecting the world.
Stem Cells and Human Development
Stem cells have enormous potential in health and medical research but to fully harness this potential, scientists are studying how stem cells transform, or differentiate, into the diverse range of specialized cells that make humans what they are today. Because diseases such as cancer or conditions such as birth defects are thought to occur because of problems in the differentiation process, an understanding of the development that happens in normal cells will help scientists treat the developmental errors that can occur.
Stem Cells and Cell-Based Therapies
Another potential application of stem cells is to form cells and tissues for medical therapies. Currently, it is donated organs and tissues that are substituted for damaged or dysfunctional ones. Sadly, the number of people awaiting a transplant is much higher than the number of available organs. Transplant waiting lists are enormous and many people die awaiting transplants. Stem cells offer a viable source of replacement cells to treat diseases and can potentially reduce the morbidity and mortality for those awaiting transplants. Some of the areas that stem cells can benefit include:
- Parkinson’s disease
- Type I diabetes
- Burn victims
- Cardiovascular diseases
By directing stem cells to differentiate into specialized cell types, there is the exciting possibility to provide a renewable source of replacement cells for those suffering from diseases.
The potential to reverse diseases is also not a foreign one. For example, a patient who has suffered from a heart attack and sustained heart damage could have the damaged tissue replaced by healthy new muscle cells. The destruction of brain cells in conditions such as Parkinson’s disease can hopefully be reversed with the replacement of new, healthy and functioning brain cells. Even more promising is the potential to address genetic defects that are present from birth by restoring function and health with the introduction of normal healthy cells that do not have these defects.
Burn victims tend to endure an enormous amount of pain from their wounds as well as frustration from the challenges of healing. Instead of donor tissues being donated, stem cells could be used to produce new and healthy tissues. This is essentially similar to therapies already being used, such as bone marrow transplants, where stem cells create different specialized blood cells. Scientists aim to locate and remove specific stem cells from a tissue and then trigger them to differentiate outside of the body before transplanting them back into the patient to replace damaged tissues. In burn victims, a very small piece of the skin can be progressively grown, allowing doctors to cover a burn that is often much larger than the original size of the skin piece.
Stem Cells and Drug Testing
Stem cells have an important benefit for the pharmaceutical field. New drugs can be tested on stem cells to assess their safety before testing drugs on animal and human models. For example, a cancer cell line could be created to test an anti-tumour drug. If the conditions can be perfectly replicated, testing drugs could provide very accurate results.
The current benefits of stem cell usage are already well documented and it is expected that continued research will pave the way for new treatments. For those suffering from serious diseases, stem cells offer hope for effective treatment or perhaps even a reversal of the disease. Time will confirm the full success of stem cell therapies and continued research should teach us more about using stem cells to treat debilitating medical conditions.
Stem Cell Research
Some diseases are treatable with stem cell therapies because scientists can regenerate some types of tissues. However, the success of the most established stem cell-based therapies—blood and skin transplants—gives hope that stem cells will allow scientists to develop therapies for a variety of diseases previously thought to be incurable.
Blood Stem Cells
After scraping a knee or donating blood, the body replenishes the blood cells that are lost by drawing on a small number of semi-specialized hematopoietic (heem-AT-oh-poh-EH-tik) stem cells contained in the blood and bone marrow. For decades, scientists have been using this type of adult stem cell to treat patients with diseases such as leukemia, sickle cell anemia, bone marrow damage, and some metabolic disorders and immunodeficiencies where the body has lost its ability to replenish its own set of healthy blood cells.
Hematopoietic stem cells give rise to all the blood cell types, from infection-fighting white blood cells to blood-clotting platelets. Preliminary results have suggested that they may also be able to produce other cell types not found in blood, but this is not yet proven. In the past, the only way to use hematopoietic stem cells for therapies was through bone marrow transplants. Extracting bone marrow is an uncomfortable and invasive procedure, and in order for a transplant to work, the donor and recipient must be genetically similar. If they are too genetically different, the blood cells produced from the transplanted marrow may recognize the patient’s body as foreign and fight against the patient’s own cells and organs. Additionally, the patient’s immune system may reject the transplant, causing a dangerous “war” within the patient’s body.
More recently, scientists have developed ways to derive hematopoietic stem cells from the blood contained in the umbilical cord and placenta at birth. The stem cells isolated from a person’s own umbilical cord blood and placenta, if used for therapies later in life, would be less likely to cause an “internal war” within the recipient’s body. They are also more accessible than the stem cells in bone marrow because the extraction of this blood poses no risk to the mother or infant.
Stem Cells Found in Umbilical Cord Blood
In 2005, the National Academies issued a report, Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program, which recommended that a national cord blood “bank” be established to harness the medical potential of this source of stem cells. Such a bank would not only benefit the people from whom the blood was collected but anyone in need of blood transplants. As with blood banks for blood transfusions, scientists could screen the bank to find the best match for each patient, providing a safer, more personalized living-cell therapy.
The Changed Face of Skin Grafts
For many years, scientists have been harnessing the regenerative capabilities of human skin to treat victims of severe burns using skin transplants. Skin transplants are possible because of the existence of stem cells located just under the top layer of skin. Every day, thousands of new skin cells are produced to replace those that have been shed. When someone suffers severe burns that destroy the source of these stem cells, their skin can no longer regenerate on its own.
Traditionally, doctors treated severe burns by transplanting sections of skin from undamaged areas of the body onto the burned areas, but if doctors could not find enough unharmed skin to cover the burned areas, the patient could die. Now, scientists can grow vast sheets of new skin by culturing the stem cells from small pieces of healthy skin. This practice, which is a type of tissue engineering, has become routine for treating burn victims over the past 20 years.
Recently, scientists have identified other types of stem cells in hair follicles and deeper layers of the skin. The inclusion of these new stem cells into engineered skin should help create more natural-looking skin transplants in the future.
Possible Future Treatment for Parkinson’s Disease?
When most people reach for a pen, their body acts in one smooth and controlled movement. This is because the instant a person thinks of grabbing the pen, a series of nerve cells fire in an orchestrated symphony from the brain to the muscles responsible for that action. For the movement to be precise and smooth, all the nerve cells in the “grabbing-the-pen network” must function properly, including cells that tell unneeded muscles to stay still.
In Parkinson’s disease, the brain cells responsible for keeping unneeded muscles from moving degenerate and die. This results in progressively more dramatic and uncontrolled movements, tremors, and spasms. To date, there is no cure for Parkinson’s disease because no one has figured out a way to bring back the specialized nerve cells that have died.
Because Parkinson’s disease results from the loss of one specific type of nerve cell, stem cells offer a very tangible possibility for treatment. Researchers have recently learned how to differentiate embryonic stem cells into the specific type of brain cell that is lost in Parkinson’s disease. They have also successfully transplanted adult nerve stem cells into rat brains. When this technique is proven to be effective and safe, transplantation of stem cells into the brains of patients may one day allow doctors to reverse the burden of Parkinson’s disease and restore control of movement.
Another strategy currently under study is the addition of chemicals or growth factors that aim to induce the patient’s own stem cells to repair the damaged nerves without needing to grow and transplant stem cells.
Possible Fix for Diabetes?
In people who suffer from type I diabetes, the beta cells of the pancreas that normally produce insulin are destroyed by the patient’s overactive immune system. Without insulin, the cells of the body cannot take up glucose and they starve. Patients with type I diabetes require insulin injections several times a day for their entire lives. The only current cure is a pancreatic transplant from a recently deceased donor, but the demand for transplants far outweighs the supply.
While adult stem cells have not yet been found in the pancreas, scientists have made progress transforming embryonic stem cells into insulin-producing cells. Combining beta-cell transplants with methods to “fix” the patient’s immune system-including chemotherapy to destroy malfunctioning immunesystem cells and blood transplants to replenish healthy white blood cells-could offer great hope for the many people suffering with type I diabetes.
Cancer: Getting to the Root of the Problem
Why are some cancers so hard to eliminate, even after many rounds of chemotherapy? The answer may lie in a few abnormal stem cells.
Cancerous stem cells were first identified in 1997 when a research group from the University of Toronto transferred a few blood stem cells from human leukemia patients into mice and watched leukemia develop in the mice. Stem cell-like cells have also recently been found in breast and brain tumors. Like normal stem cells, tumor stem cells exist in very low numbers, but they can replicate and give rise to a multitude of cells. Unlike normal stem cells, however, cancerous stem cells lack the controls that tell them when to stop dividing. Traditional chemotherapy kills off the majority of the tumor cells, but if any of the cancerous stem cells survive the treatment, the cancer may return. Research into the differences in gene expression between normal and tumor stem cells may lead to treatments where the root of the problem—the cancer stem cell—is targeted.
Are the Promises of Stem Cell Therapies Realistic?
The list of medical achievements stem cells could offer seems to be expanding at an incredible pace. The role of stem cells in medicine is already very real, but there is a danger of exaggerating the promise of new medical developments.
What tend to be “over-promised” are not only the potential outcomes of both embryonic and adult stem cell research, but also the time scales that are involved. The basic research needed to develop viable therapeutic options is a lengthy process that may extend over many years and decades. Even after science has moved from basic research to developing medical applications, it still takes many years to thoroughly test those applications and demonstrate that they are safe to prescribe for patients. This is true for all medical treatments, including the development of new drugs, procedures, and medical equipment, and is not specific to the living cell therapies made possible by stem cell research.
There are also many legal and social questions that must be addressed before stem cell-based therapies become clinically available. Legal issues that will affect stem cell applications include how to address intellectual property concerns and how to apply and enforce diverse and sometimes conflicting state and national laws. Social issues include concerns about the destruction of embryos, the distribution of the benefits of the research, and the protection of both physical and privacy interests of egg and sperm donors and clinical research subjects.
The Role of Stem Cells in Basic Research
Stem cells offer opportunities for scientific advances that go far beyond regenerative medicine. They offer a window for addressing many of biology’s most fundamental questions.
Watching embryonic stem cells give rise to specialized cells is like peeking into the earliest development of the many tissues and organs of the human body. Stem cell research may help clarify the role genes play in human development and how genetic mutations affect normal processes. They can be used to study how infectious agents invade and attack human cells, to investigate the genetic and environmental factors that are involved in cancer and other diseases, and to decipher what happens during aging.
Stem cells may also revolutionize traditional chemical medicine. Because embryonic stem cells can continue to divide for long periods of time and produce a variety of cell types, they could provide a valuable source of human cells for testing drugs or measuring the effects of toxins on normal tissues without risking the health of a single human volunteer. In the future, thousands of compounds could be quickly tested on a wide assortment of cell types derived from stem cells, making drug discovery more efficient and cost effective.
Using nuclear transfer to produce stem cells could be particularly useful for testing drugs for disorders that are of genetic origin. For example, it is difficult to study the progression of Alzheimer’s and Parkinson’s diseases in the brains of live patients- but by using the cells of an Alzheimer’s patient to create stem cell lines with nuclear transfer, scientists could trace the development of the disease in a culture dish and test drugs that regenerate lost nerve cells with no danger to the patient.
Stem cells may also help scientists calculate the effects of toxic substances in drugs, food, and the environment.
What to Ask in a Stem Cell Clinic?
Listed below are a series of questions to ask a clinic from which you are considering receiving a stem cell treatment. You have the right to know as much information as possible about the procedure, the science that supports it, the costs, the expected outcome and any possible risks. The doctors involved should know a lot about your disease or condition, other treatment options, and the evidence that the treatment they are offering will be safe and that it will work.
The questions and answers are best discussed with a trusted physician familiar with your condition who can help you understand the treatment and your choices. We encourages patients and their families to seek medical advice independent of the provider to help assess whether the treatment and outcome claims offered are reasonable.
Is the treatment routine for this specific disease or condition?
Is the treatment part of a formal clinical trial?
What are the alternative treatment options for my disease or condition?
If I have this treatment, could it affect whether I get into another clinical trial or am I able to have another treatment?
What are the possible benefits I can expect? How will this be measured and how long will this take?
What other medications or special care might I need?
How is this stem cell procedure done?
What is the source of the stem cells?
How are the stem cells identified, isolated and grown?
Are the cells differentiated into specialized cells before therapy?
How are the cells delivered to the right part of the body?
If the cells are not my own, how will my immune system be prevented from reacting to the transplanted cells?
Scientific evidence and oversight
What is the scientific evidence that this new procedure could work for my disease or condition? Where is this published?
Have there been (earlier) clinical trials? What was learned from these trials?
Is there independent oversight of the treatment plan, for example, an Institutional Review Board? Can you provide me with several names of scientists and clinicians who can give me independent advice?
Is there any independent oversight or accreditation of the clinic where the treatment will be done and the facility where the cells are processed?
Is there approval from national or regional regulatory agency, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA), for this treatment of this specific disease?
Safety and emergencies
What are the risks of the procedure itself, and the possible side effects both immediate and long-term?
Are there any other risks to me in joining in the study?
What will be done if an adverse reaction (bad side-effect) develops? Who is the person to contact in an emergency or research-related injury? Who will provide emergency medical care?
Is the clinic adequately prepared to handle emergencies such as a serious allergic reaction?
What follow-up treatment will be received, and for how long? What will I need to do?
Who is the doctor in charge of the treatment? What specialized training does this doctor have? How well trained are the other doctors and the technical support staff?
What are my rights as a participant—for example confidentiality, my right to be informed of any new information that might come up, my right to withdraw from the treatment process?
What compensation am I entitled to if I am injured as a result of taking part in this study?
What are the costs of the treatment? What does this include? What other costs will I incur?
What would be the costs of emergency treatment if something goes wrong? Who would provide this and pay for this? Before traveling or agreeing to treatment, find out what costs your travel insurance, health insurance provider or national program will cover, in what circumstances and in what countries.
How Stem Cells Clinical Trials Work
A clinical trial is a research study designed to answer specific questions about a new treatment or a new way of using current treatments. Clinical trials are used to establish whether new treatments are safe and effective. It is very important to understand that the new treatment may not be better than, or even as good as, existing treatments.
Most drugs and treatments that are widely accepted by the medical community have been tested in clinical trials. If a trial is successful, meaning the treatment is shown to be both safe and effective, the experimental treatment can become standard treatment.
Clinical Trials Are Not All Equal
A clinical trial may be at a different stage—for example, testing safety, dosage, or effectiveness. Also, although the types of patient protections are widely accepted and employed in the design of clinical trials, there may be a wide range in the quality of clinical trials and the scientific evidence supporting them. Discuss any clinical trials you may be considering with a trusted physician.
There Are Four Stages of Testing in Clinical Trials
- In phase I trials, a small group of people is tested. The goal of such trials is to determine the safe dosage range and to identify the side effects of a drug or treatment. Therapeutic benefit, while not excluded, is not the primary goal of this initial phase of clinical testing. If a treatment has unacceptable side effects at this stage, further trials are not initiated.
- Next are phase II trials. A larger group of patients is treated based on the findings of the phase I trial. Here, investigators test whether a treatment is effective, while they continue to monitor side effects.
- In a phase III trial, a larger group of patients is treated to confirm effectiveness compared to standard treatment(s).
- Phase IV trials happen after a drug has made it to the market, and serve as a follow-up to examine effectiveness and side-effects on very large patient populations. It can happen that rare but serious side effects are only detected during large phase IV trials.
A typical clinical trial has an experimental treatment group, which consists of patients receiving an experimental treatment, while another group serves as the control group. The results in the experimental treatment group are compared to the control group to determine the effect of the treatment. In most cases the control group receives a standard treatment for the disease. If there is no standard treatment, the group may receive no intervention. Sometimes evidence gathered from historical studies can serve as the control group.
The results of these trials are analyzed using statistics to determine whether any difference between the groups might be due to coincidence or placebo effect. Whenever possible, clinical trials are “double blind”. This means that neither the physician nor patient knows who gets the new treatment, and who does not. However, this is not always feasible.
Oversight and Informed Consent
A further characteristic of clinical trials is oversight, both at the local level (the treating hospital or institution) and in many countries at the government level (for example, the European Medicines Agency (EMA) or the U.S. Food and Drug Administration). Oversight at multiple levels promotes the scientific validity of the experimental treatment, and protects the patients. One requirement is appropriate informed consent. This means that the patients are informed about the goal, duration, potential risks and nature of the treatment. It is important to realize that while participating in a clinical trial may benefit the patient, there is no guarantee that this will be the case, as these trials are undertaken firstly to test whether or not a treatment is safe; and if it is safe whether or not it offers any benefit. Furthermore, unexpected side effects may occur. If these are serious, the trial will be stopped.