Stem cells help to create new cells in existing healthy tissues, and may help repair tissues in areas that are injured or damaged. They are the basis for the specific cell types that make up each organ in the body. Stem cells are distinguished from other cells by a few important characteristics: they have the ability to self-renew; they have the ability to divide for a long period of time; and, under certain conditions, they can be induced to differentiate into specialized cells with distinct functions (phenotypes) including, but not limited to, cardiac cells, liver cells, fat cells, bone cells, cartilage cells, nerve cells, and connective tissue cells. The ability of cells to differentiate into a variety of other cells is termed multipotency. What scientists learn about controlling stem cell differentiation can become the basis for new treatments of many serious diseases and injuries.
Some organs contain stem cells, called adult stem cells, that persist throughout life and contribute to the maintenance and repair of those organs. Not every organ has been shown to contain these cells, and generally adult stem cells have restricted developmental potential, in that their capacity for proliferation is limited and they can give rise only to a few cell types. Embryonic stem cells, by contrast, can divide almost indefinitely and can give rise to every cell type in the body, suggesting that they may be the most versatile source of cells for research and transplantation therapy.
There are several sources of stem cells used in research. Embryonic stem cells are obtained from the inner cell mass of a blastocyst. The blastocyst is formed when the fertilized egg, or zygote, divides and forms two cells, then again to form four, and so on until it becomes a hollow ball of about 150 cells. The ball of cells, now called the blastocyst, actually contains two types of cells — the trophoblast, and the inner cell mass. The inner cell mass contains the pluripotent stem cells that can be isolated and cultured. Stem cells are also found in differentiated tissues and organs throughout the body. Often referred to as adult stem cells, or tissue-specific cells, they have not been identified in all tissues and organs, but in many cases they do exist and have a confirmed roll in repairing and maintaining tissue that has been injured or damaged by disease. The adult stem cells can be isolated from samples of the tissue, with the cells suspended in liquid and separated based on cell surface markers using fluorescence activated cell sorting (FACS). Blood from the umbilical cord of a newborn baby also contains blood stem cells and is often harvested and banked for future use, either for the benefit of research or for future treatments that the donor may require. The amniotic fluid is another rich source of stem cells that are multipotent and often more robust than stem cells derived by other means. Lastly, induced pluripotent stem cells (iPS cells) can be derived from the large pool of differentiated cells in the body (e.g. skin, fat, muscle, etc), which are transformed into an embryonic-like stem cell state.
Induced pluripotent cells are derived from somatic (adult, non-germline) cells, which have been reverted to an embryonic stem cell-like state. Like embryonic stem cells, iPS cells can be differentiated into any cell in the body, and are therefore considered pluripotent. The process of creating these cells, often referred to as “reprogramming,” involves introducing a combination of three to four genes for transcription factors delivered by retroviruses into the somatic cell. More recent methods have replaced and reduced the number of genes required for the transformation, used alternative delivery methods to get the genes into the cell, or sought to replace the genes with chemical factors. Cells can be taken from patients with specific diseases such as ALS, Parkinson’s, or cardiovascular disease and induced to form iPS cells. Multiple uses can be derived from iPS cells when they are differentiated to more specialized cell types, including the development of assays for studying disease processes, scanning drug candidates for safety and effectiveness, or application to regenerative medicine.
Adult stem cells are most commonly obtained from the outside part of the pelvis, the iliac crest. A needle is inserted in the iliac bone and bone marrow is withdrawn or aspirated through the needle. Several samples may be obtained from one area in this manner. The stem cells may then be separated from other cells in the marrow and grown or expanded in the laboratory. This may take from 7 to 21 days. When stem cells are placed in a specific tissue environment, such as bone, they become activated. As they divide, they create new stem cells and second generation, progenitor cells. It is the progenitor cells which may differentiate into newer cells with the same phenotype as the host tissue.
Stem cell researchers are hopeful that, in the future, a wide range of diseases and traumatic injuries will be cured by some application of cell therapy using stem cells. Currently, donated organs and tissues are used to replace lost or damaged tissue in many disorders. The great regenerative potential of stem cells has created intense research involving experiments aimed at replacing tissues to treat Parkinson’s and Alzheimer’s diseases, osteoarthritis, rheumatoid arthritis, spinal cord injury, stroke, burns, heart disease, and diabetes. While some success has been achieved with laboratory animals, a very limited number of experiments have been conducted on humans. These few experiments, however, have shown the great potential for stem cells. Scientists believe that a deep understanding of the complex phenomenon of stem cell differentiation will lead to a potential cure for serious medical conditions that are caused by abnormal cell division and differentiation, such as cancer and several growth and development disorders. Another reason why stem cell biologists are excited about this field is that human stem cells could also be used to test new drugs. For example, new medications could be tested for safety by applying them to specialized cells differentiated from a stem cell clone. Cancer treatment, for instance, could benefit tremendously if anti-tumor drugs could be tailored to target the tumor stem cell.
At this point, most musculoskeletal treatments using stem cells are performed at research centers as part of controlled clinical trials. Stem cell procedures are being developed to treat bone fractures and nonunions, regenerate articular cartilage in arthritic joints, and heal ligaments or tendons. These are detailed below. Bone fractures and nonunions: In bone, progenitor cells may give rise to osteoblasts, which become mature bone cells, or osteocytes. Osteocytes are the living cells in mature bone tissue. Stem cells may stimulate bone growth and promote healing of injured bone. Traditionally, bone defects have been treated with solid bone graft material placed at the site of the fracture or nonunion. Stem cells and progenitor cells are now placed along with the bone graft to stimulate and speed the healing. Articular cartilage: The lining of joints is called the articular cartilage. Damage to the articular cartilage can frequently lead to degeneration of the joint and painful arthritis. Current techniques to treat articular cartilage damage use grafting and transplantation of cartilage to fill the defects. It is hoped that stem cells will create growth of primary hyaline cartilage to restore the normal joint surface. Ligaments and tendons: Mesenchymal stem cells may also develop into cells that are specific for connective tissue. This would allow faster healing of ligament and tendon injuries, such as quadriceps or Achilles tendon ruptures. In this instance, stem cells would be included as part of a primary repair process.
Stem cells have potential in many different areas of health and medical research. To start with, studying stem cells will help us to 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.
It’s hard work. First, cells must be coaxed into becoming the desired cell types. That process is called differentiation. For example, researchers have successfully used chemicals to turn embryonic stem cells into neurons, beating heart cells, insulin-producing islet cells and others. But the process of differentiation for the myriad cells in the human body is an extremely complicated one that scientists are only beginning to understand. Getting the cells to do what doctors want once they’re inside the body is a huge challenge. Second, scientists have to find a way to prevent cells from being rejected by a patient’s immune system. For some therapies, matching the cells to patients could be similar to the way doctors match bone marrow when performing transplants.
Some of the promise of stem cell therapy has been realized. A prime example is bone marrow transplantation. Even here, however, many problems remain to be solved. Challenges facing stem cell therapy include the following: Adult stem cells Tissue-specific stem cells in adult individuals tend to be rare. Furthermore, while they can regenerate themselves in an animal or person they are generally very difficult to grow and to expand in the laboratory. Because of this, it is difficult to obtain sufficient numbers of many adult stem cell types for study and clinical use. Hematopoietic or blood-forming stem cells in the bone marrow, for example, only make up one in a hundred thousand cells of the bone marrow. They can be isolated, but can only be expanded a very limited amount in the laboratory. Fortunately, large numbers of whole bone marrow cells can be isolated and administered for the treatment for a variety of diseases of the blood. Skin stem cells can be expanded however, and are used to treat burns. For other types of stem cells, such as mesenchymal stem cells, some success has been achieved in expanding the cells in vitro, but application in animals has been difficult. One major problem is the mode of administration. Bone marrow cells can be infused in the blood stream, and will find their way to the bone marrow. For other stem cells, such as muscle stem cells, mesenchymal stem cells and neural stem cells, the route of administration in humans is more problematic. It is believed, however, that once healthy stem cells find their niche, they will start repairing the tissue. In another approach, attempts are made to differentiate stem cells into functional tissue, which is then transplanted. A final problem is rejection. If stem cells from the patients are used, rejection by the immune system is not a problem. However, with donor stem cells, the immune system of the recipient will reject the cells, unless the immune system is suppressed by drugs. In the case of bone marrow transplantation, another problem arises. The bone marrow contains immune cells from the donor. These will attack the tissues of the recipient, causing the sometimes deadly graft-versus-host disease. Pluripotent stem cells All embryonic stem cell lines are derived from very early stage embryos, and will therefore be genetically different from any patient. Hence, immune rejection will be major issue. For this reason, iPS cells, which are generated from the cells of the patient through a process of reprogramming, are a major breakthrough, since these will not be rejected. A problem however is that many iPS cell lines are generated by insertion of genes using viruses, carrying the risk of transformation into cancer cells. Furthermore, undifferentiated embryonic stem cells or iPS cells form tumors when transplanted into mice. Therefore, cells derived from embryonic stem cells or iPS cells have to be devoid of the original stem cells to avoid tumor formation. This is a major safety concern. A second major challenge is differentiation of pluripotent cells into cells or tissues that are functional in an adult patient and that meet the standards that are required for ‘transplantation grade’ tissues and cells. A major advantage of pluripotent cells is that they can be grown and expanded indefinitely in the laboratory. Therefore, in contrast to adult stem cells, cell number will be less of a limiting factor. Another advantage is that given their very broad potential, several cell types that are present in an organ might be generated. Sophisticated tissue engineering approaches are therefore being developed to reconstruct organs in the lab. While results from animal models are promising, the research on stem cells and their applications to treat various human diseases is still at a preliminary stage. As with any medical treatment, a rigorous research and testing process must be followed to ensure long-term efficacy and safety.
Adult stem cell-based therapies are already in widespread clinical use and have been for over 40 years, in the form of bone marrow transplants. These procedures, used to teat leukemia, lymphoma and inherited blood disorders, save many lives every year, and demonstrate the validity of stem cell transplantation as a therapeutic concept. New clinical applications are being explored using stem cells for the treatment of multiple sclerosis, cardiavascular disease, stroke, autoimmune and metabolic disorders, and chronic inflammatory diseases in addition to blood cancers. While human clinical trials have begun in many of these applications, it may still be a matter of years before these treatments become widely available to the patient. Nevertheless, we are optimistic that successes will be possible, and that new stem cell based treatments will become available as they complete clinical trials.
That remains to be seen. Potential dangers include:
- As stem cells renew themselves and can become different kinds of cells, they might become cancer cells and form tumors.
- Stem cells grown in the laboratory, or adult cells reprogrammed to be stem cells, might have genetic damage.
There is also risk in some of the procedures used to get stem cells out of the body (such as from liposuction or spinal tap) or to deliver stem cells to the body (such as implanting them in the heart, brain, spinal cord, or other organs). That’s not so much about the stem cells, but because of the procedures themselves. Researchers are studying all of that. Without carefully controlled clinical trials, there’s no way to know what might happen in the long term, or even in the short term. That’s why the FDA discourages the use of stem cells except in clinical trials or approved therapies. Every medical procedure has risks. A goal of clinical trials is to determine whether the potential benefit of a treatment outweighs the risks. A possible risk of some stem cell treatments may be the development of tumors or cancers. For example, when cells are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth. A particular danger of pluripotent cells is that, if undifferentiated, they may form tumors called teratomas. Other possible risks include infection, tissue rejection, and complications arising from the medical procedure itself.
While your own cells are less likely to be rejected by your immune system, this does not necessarily mean the cells are safe to use as a therapeutic treatment. The methods used to isolate, modify, grow or transplant the cells may alter the cells, could cause infection or introduce other unknown risks. Transplanting cells into a different part of the body than they originated from may have unforeseen risk, complications or unpredictable outcomes.
Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Receiving an unproven treatment may make a person ineligible to participate in upcoming clinical trials. Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends.
Many clinics from all over the world offer stem cell therapies for a variety of diseases. However, many of these treatments are unproven, and in addition, these treatments tend to be very expensive.
Stem cells can be used to generate cell lines specific to a particular patient with a particular disease. By matching the biological data from these cells with the clinical history of the patient, it may be possible to extract more relevant information on the linkage between molecular pathways and the causes of disease. Cell lines can be derived from stem cells for specific tissues, such a heart muscle, specific types of neurons, kidney cells, etc. and used in biological assays to screen thousands of chemical compounds for their safety and effectiveness in treating disease. Stem cells also play an important role in expanding our understanding of embryonic and fetal development, helping us to identify the cells and molecules responsible for guiding the patterns of normal (and abnormal) tissue and organ formation.