Why is stem cell therapy not approved in the United States?
It’s surprising how many Americans are going abroad for autologous stem cell treatments (using cells from a patient’s own body not embryonic stem cells). Why are autologous stem cell treatments not available in the United States?
The reason is the U.S. Food and Drug Administration categorized an autologous stem cell transplant as it would a drug. Therefore autologous stem cell transplants must go through the same rigorous phase trials that a new drug would which has added years to the approval process. Some experts feel it will take from 7 to 10 years before this will occur in the United States.
From the FDA Regulation of Stem-Cell–Based Therapies in the New England Journal of Medicine:
“Any stem-cell–based product that contains cells or tissues that “are highly processed, are used for other than their normal function, are combined with non-tissue components, or are used for metabolic purposes” would also be subject to the Public Health Safety Act, Section 351, which regulates the licensing of biologic products and requires the submission of an investigational new drug application to the FDA before studies involving humans are initiated.”
While this is the FDA’s ruling on autologous stem cell transplantation, others disagree with this assessment. Their view is because the stem cells used in this procedure are the patient’s own cells, removed from the patient, treated and then replaced in the same patient, they should not be considered a drug.
From a press release from the American Stem Cell Therapy Association (ASCTA):
“Many patients are dying or suffering daily with incurable diseases or problems that require major surgery. These patients should have access to basic adult stem cell therapy now.” stated Christopher J. Centeno, M.D, an ASCTA physician member. “ASCTA is establishing guidelines which will allow the safe use of the patient’s own adult stem cells under the supervision of doctors.” continued Centeno. Another ASCTA physician member, Frank Falco, M.D. stated, “The FDA’s position against someone using their own stem cells is taking it too far. We are talking about a person using their own tissue to treat a degenerative disorder or process safely without the use of medications or surgery. Although we agree that oversight and standards are necessary, this should be provided through a physician organization such as ASCTA rather than by a government agency.”
While the FDA continues it’s rigorous phase trials of autologous stem cell transplantation therapy, the only choice patients have who would benefit from treatment is to go outside of the United States to receive it.
What are stem cells?
Stem cells are the foundation cells for every organ, tissue and cell in the body. They are like a blank microchip that can ultimately be programmed to perform particular tasks. Stem cells are undifferentiated or “blank” cells that have not yet fully specialized. Under proper conditions, stem cells begin to develop into specialized tissues and organs. Additionally, stem cells can self-renew, that is they can divide and give rise to more stem cells.
There are many different types of stem cells. These include embryonic stem cells that exist only at the earliest stages of embryonic development; as embryonic stem cells can form all cell types of the body, they are referred to as ‘pluripotent’ stem cells. There are various types of ‘adult’ or ‘tissue-specific’ stem cells that exist in a number of different fetal and adult tissues. These stem cells generally can only form a limited number of cell types corresponding with their tissues of origin; they are called ‘multipotent’ stem cells.
Where do stem cells come from?
Embryonic stem cells are derived from the inner cell mass of a blastocyst: the fertilized egg, called the zygote, divides and forms two cells; each of these cells divides again, and so on. Soon there is a hollow ball of about 150 cells called the blastocyst that contains two types of cells, the trophoblast and the inner cell mass. Embryonic stem cells are obtained from the inner cell mass.
Stem cells can also be found in small numbers in various tissues in the fetal and adult body. For example, blood stem cells are found in the bone marrow that give rise to all specialized blood cell types. Such tissue-specific stem cells have not yet been identified in all vital organs, and in some tissues like the brain, although stem cells exist, they are not very active, and thus do not readily respond to cell injury or damage.
Stem cells can also be obtained from other sources, for example, the umbilical cord of a newborn baby is a source of blood stem cells. Recently, scientists have also discovered the existence of cells in baby teeth and in amniotic fluid that may also have the potential to form multiple cell types. Research on these cells is at a very early stage.
Recently, cells with properties similar to embryonic stem cells, referred to as induced pluripotent stem cells (iPS cells) have been engineered from somatic cells (see ‘What is are induced pluripotent stem cells?’).
What is a stem cell line?
A stem cell line is a population of cells that can replicate themselves for long periods of time in vitro, meaning outside of the body. These cell lines are grown in incubators with specialized growth factor-containing media (liquid food source), at a temperature and oxygen/carbon dioxide mixture resembling that found in the mammalian body.
What is an embryonic stem cell?
Embryonic stem cells are those grown from the cells that make up the inner cell mass of the blastocyst. Embryonic stem cells have been derived from a variety of animals, including human, and are described as ‘pluripotent’- that is, they are capable of generating any and all cells in the body under the right conditions.
Embryonic stem cell lines can be grown indefinitely in vitro if the correct conditions are met. Importantly, these cells continue to retain their ability to form different, specialized cell types once they are removed from the conditions that keep them in an undifferentiated, or unspecialized, state.
The most widely studied are mouse embryonic stem cells. Mouse embryonic stem cells have taught us a lot about how pluripotent cells grow and specialize, and how embryonic development works. Indeed, mouse embryonic stem cells are a critical research tool for studying the function of individual genes and modeling human diseases. Mouse embryonic stem cells can be manipulated to contain specific genetic changes then used to generate mice which contain this change. Capecchi, Evans and Smithies were awarded the Nobel Prize in Physiology or Medicine, 2007 for developing this process.
Human embryonic stem cells were isolated relatively recently, in 1998. They are more difficult to work with than their mouse counterparts and currently less is known about them. However, scientists are making remarkable progress, learning about human developmental processes, modeling disease and establishing strategies that could ultimately lead to therapies to replace or restore damaged tissues using these human cells.
What is an adult (tissue-specific) stem cell?
Perhaps better referred to as a tissue-specific stem cell, these cells are found in tissues that have already developed. Tissue-specific stem cells can be isolated from many tissues, including brain. The most common source of tissue-specific stem cells is the bone marrow, located in the center of some bones. There are different types of stem cells found in the bone marrow, including hematopoietic or blood stem cells, endothelial stem cells, and mesenchymal stem cells. It is well established that hematopoietic stem cells form blood, that endothelial stem cells form the vascular system (arteries and veins), and that mesenchymal stem cells form bone, cartilage, muscle, fat, and fibroblasts.
While it has been theorized that some adult stem cells may have a broader potential to form different cell types than was previously suspected (for example, cells from the bone marrow may contribute to regeneration of damaged livers, hearts and other organs), this is highly controversial in the scientific community. Currently, it is not clear whether stem cells from adult tissues or umbilical cord blood are truly pluripotent. The comparison of human embryonic stem cells to adult stem cells is currently a very active area of research.
What are 'induced pluripotent cells' or IPS cells?
Induced pluripotent cells (iPS cells) are non-pluripotent cells that were engineered (‘induced’) to become pluripotent, that is, able to form all cell types of the body. In other words, a cell with a specialized function (for example a skin cell) was ‘reprogrammed’ to an unspecialized state similar to that of an embryonic stem cell. While iPS cells and embryonic stem cells share many characteristics they are not identical.
The generation of mouse iPS cells was reported in 2006. Currently, iPS cells are produced by inserting copies of three-four genes into specialized cells known to be important in embryonic stem cells using viruses. Different groups have used slightly different combinations of genes. It is not completely understood how each of these genes functions to confer pluripotency and ongoing research is addressing this question.
The technology used to generate iPS cells holds great promise for creating patient- and disease-specific cell lines for research purposes. However, a great deal of work remains before these methods can be used to generate stem cells suitable for safe and effective therapies.
What are the potential uses of human stem cells?
Stem cell research contributes to a fundamental understanding of how organisms develop and grow, and how tissues are maintained throughout adult life. This is knowledge that is required to work out what goes wrong during disease and injury and ultimately how these conditions might be treated. The development of a range of human tissue-specific and embryonic stem cell lines will provide researchers with the tools to model disease, test drugs and develop increasingly effective therapies.
Replacing diseased cells with healthy cells, a process called cell therapy, is a promising use of stem cells in the treatment of disease; this is similar to organ transplantation only the treatment consists of transplanting cells instead of organs. Currently, researchers are investigating the use of adult, fetal and embryonic stem cells as a resource for various, specialized cell types, such as nerve cells, muscle cells, blood cells and skin cells that can be used to treat various diseases.
In theory, any condition in which there is tissue degeneration can be a potential candidate for stem cell therapies, including Parkinson’s disease, spinal cord injury, stroke, burns, heart disease, Type 1 diabetes, osteoarthritis, rheumatoid arthritis, muscular dystrophies and liver diseases.
In addition, retinal regeneration with stem cells isolated from the eyes can lead to a possible cure for damaged or diseased eyes and may one day help reverse blindness. Bone marrow transplantation (transfers blood stem cells) is a well-established treatment for blood cancers and other blood disorders.
What are the obstacles that must be overcome before the potential uses of stem cells in cell therapy will be realized?
Here are just a few of the challenges that lie ahead. Firstly, a source of stem cells must be found. The process of identifying, isolating and growing the right kind of stem cell, for example a rare cell in the adult tissue, is painstaking. In general, embryonic and fetal stem cells are believed to be more versatile than tissue-specific stem cells. Secondly, once stem cells are identified and isolated, the right conditions must be developed so that the cells differentiate into the specialized cells required for a particular therapy. This too will require a great deal of experimentation. Thirdly, a system that delivers the cells to the right part of the body must be developed and the cells once there, must be encouraged to integrate and function in concert with the body’s natural cells. Furthermore, just as in organ transplants, the body’s immune system must be suppressed to minimize the immune reaction set off by the transplanted cells.
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.
Are stem cells currently used in therapies today?
Hematopoietic stem cells (HSCs) or blood stem cells, present in the bone marrow are the precursors to all blood cells. Blood stem cells are currently the only type of stem cells commonly used for therapy. Doctors have been transferring blood stem cells by bone marrow transplant for more than 40 years. Advanced techniques for collecting or “harvesting” HSCs are now used to treat leukemia, lymphoma and several inherited blood disorders. Cord blood, like bone marrow, is stored as a source of HSCs and is being used experimentally as an alternative to bone marrow in transplantation.
New clinical applications for stem cells are currently being tested therapeutically for the treatment of musculoskeletal abnormalities, cardiac disease, liver disease, autoimmune and metabolic disorders (amyloidosis), chronic inflammatory diseases (lupus) and other advanced cancers. However, these new therapies have been offered only to a very limited number of patients.
Why is cord blood a valuable resource?
Cord blood is rich in hematopoietic or blood stem cells and is currently being used as an experimental alternative to bone marrow transplantation. The collection process is completely non-invasive, the host-donor match required for transplantation is less stringent and cord blood has fewer mature immune cells and thus poses a lower risk of graft vs. host disease.
Why are researchers interested in developing disease-specific or patient-specific pluripotent stem cells?
The development of patient-specific or disease-specific pluripotent stem cells has great therapeutic promise for three reasons. Firstly, these cells could provide a powerful new tool for studying the basis of human disease and for discovering new drugs. Secondly, the resulting embryonic stem cells could be developed into a needed cell type, and if transplanted into the original donor, would be recognized as ‘self’, thereby avoiding the problems of rejection and immunosuppression that occur with transplants from unrelated donors.
What is somatic cell nuclear transfer (SCNT)?
Somatic cell nuclear transfer (SCNT) is a technique in which the nucleus of a somatic cell, that is any cell of the body apart from the sperm or egg, is transferred into an egg that has had its original nucleus removed. The egg now has the same DNA, or genetic material, as the donor somatic cell. Given the right signals, the egg can be coaxed into developing as if it had been fertilized. The egg would divide to form 2 cells, then 4 cells, then 8 cells and so on until the blastocyst is formed. Embryonic stem cells can be derived from this blastocyst to create cell lines that are genetically identical to the donor somatic cell.
Why derive embryonic stem cell lines following somatic cell nuclear transfer (SCNT)?
The derivation of patient-specific human embryonic stem cell lines using this technique (see ‘What is somatic cell nuclear transfer?’) Firstly, these cells could provide a powerful new tool for studying the basis of human disease and for discovering new drugs. Secondly, the resulting embryonic stem cells could be developed into a needed cell type, and if transplanted into the original donor, would be recognized as ‘self’, thereby avoiding the problems of rejection and immunosuppression that occur with transplants from unrelated donors.
Can induced pluripotent cells replace research on embryonic stem cells or somatic cell nuclear transfer?
No. The derivation of human induced pluripotent stem cells opens up exciting new areas of stem cell research, however, this technology is at a very early stage and many fundamental questions remain. While iPS cells and embryonic stem cells share many characteristics they are not identical. The similarities and differences are still being explored.
Research on human embryonic stem cells, somatic cell nuclear transfer and ‘adult’ or tissue-specific stem cells needs to continue in parallel. All are part of a research effort that seeks to expand our knowledge of how cells function, what fails in the disease process, and how the first stages of human development occur. It is this combined knowledge that will ultimately generate safe and effective therapies.
What is reproductive cloning?
If an egg generated by somatic cell nuclear transfer (see ‘What is somatic cell nuclear transfer?’) was implanted into the womb of an animal, an individual would be born that has identical genetic material as the donor somatic cell and might be referred to as a ‘clone’. The procedure is referred to as ‘reproductive cloning’ and is fraught with profound technical and biological problems. The overwhelming consensus of the world’s scientific and medical communities is that at this time human reproductive cloning should be banned.
What is regenerative medicine?
The goal of regenerative medicine is to repair organs or tissues that are damaged by disease, aging or trauma, such that function is restored, or at least improved.
The term regenerative medicine is often used nowadays to describe medical treatments and research that use stem cells (either adult or embryonic) to restore the function of organs or tissues. This can be achieved in different ways; first, by administering stem cells, or specific cells that are derived from stem cells in the laboratory; or second, by administering drugs that coax stem cells that are already present in tissues to more efficiently repair the involved tissue.
What is bioethics?
Bioethics is the study of the moral and ethical issues in the fields of scientific research, medical treatment and, more generally, in the life sciences. With advancing technology come new and exciting insights into scientific processes and diseases; at the same time, new ethical issues arise.