Does the Potential Outweigh the Opposition
Jonathan Yoder
Goshen College, Goshen, IN
Professor Stan Grove, PhD.
22 November, 2006
Thesis
The current and potential benefits of stem cell use in medical therapies makes stem cell research an important field that should continue to be pursued.
Outline
Stem Cell Research: What's the Controversy?
I. Intro
a. History
b. What are stem cells
i. Adult
ii. Embryonic
c. How are they obtained
i. Immortal cell lines
ii. Left over from IVF (donated)
a. Cell-based therapies: Replacement of tissue through cultured stem cell lines
i. diabetes
ii. heart disease
iii. treatment of neurological disease
iv. spinal cord injury
b. Drug Testing
III. Criticism/Opposition
a. Religious views
b. Suggested alternatives
IV. Conclusion
As medical science advances, new technologies are developed that have amazing potential in the treatment or possible elimination of numerous diseases that were once considered devastating to the individual and incurable. One of these new and developing technologies is the use of stem cells. Stem cells harbor enormous potential that is not yet completely understood. However, there is a general controversy surrounding the development of the use of stem cells. In order to understand this controversy a more in depth look into the area of stem cell research is required.
Stem cells have actually been used in medical therapies for quite some time. It was first discovered by European scientists in the early 1900's that all blood cells come from one specific precursor or "stem cell". A common use of the transplantation of stem cells is in the treatment of leukemia and other diseases or a bone marrow transplant. It wasn't until 1998 that James Thomson from the University of Wisconsin isolated and successfully cultured embryonic stem cells, followed by James Gearhart at John's Hopkins University who cultivated stem cells from human germ cells. Shortly after that it was discovered that in mice, manipulation of adult tissue could produce unsuspected tissue types: such as bone marrow cells producing nerve or liver cells (Lasker Foundation, 2001). More recently, stem cells have been shown to have possibilities of treating numerous diseases ranging from diabetes to Alzheimer's and even spinal injuries. It is this vast potential to help some of the most devastating diseases and injuries that makes the pursuit of stem cell research an important avenue of research.
Stem cells are unspecialized cells in the body that are capable of dividing and renewing themselves for long periods that can give rise to any of the other specialized cells. As unspecialized cells this means that a stem cell by itself does not contain any tissue specific structures that would for example allow it to transport oxygen through the blood like a red blood cell or produce electrochemical signals as does a nerve cell. Because it is unspecialized however, it maintains the potential for development into these specialized cell lines of muscle, blood, nerve, etc (NIH, Stem Cell Basics, 2006). The second property that makes stem cells unique is, unlike muscle, blood or nerve cells, stem cells can proliferate, yielding millions of unspecified cells, making them capable of long-term self-renewal. Cells can be categorized into totipotent, pluripotent or unipotent. Totipotent cells have the capability to generate all the cells and tissue that make up a human embryo and support it during development, it has the total potential to become a complete organism. Pluripotent cells have the potential become any cell type derived from one of the embryonic germ layers: endoderm, mesoderm, and ectoderm. Unipotent cells only have the potential to differentiate along one cell lineage (only blood cells, nerve cells, etc.) (NIH, 2001).
Stem cells are either pluirpotent or unipotent and play an important role in the development of organisms (NIH, 2001). It is stem cells that, after stimulation by specific signals then differentiate into the various types of tissue during development. Stem cells also play a role in tissue repair in adults. For example, upon the proper signal, stem cells in bone marrow differentiate into the various types of blood cells; red, white, platelets etc. The signaling process that triggers this differentiation is not well understood as a myriad of factors play a part from the cells own DNA to chemicals secreted by other cells to even physical contact with neighboring cells (NIH, Stem Cell Basics, 2006). It is this process that is under investigation into learning how to trigger stem cells to differentiate into a desired type of cell.
There are two types of stem cells, embryonic and adult. Embryonic stem cells come from embryos, as their name suggests. They are derived from embryos from eggs fertilized in vitro and donated for research purposed. These embryos are typically 4-5 days old and consist simply of a hollow ball of cells called a blastocyst (NIH, 2001). These can come from embryos specifically created and donated for these purposes or in many cases from embryos that are the byproduct of In-vitro Fertilization, IVF, techniques, in which several embryos are created and the most viable ones selected and implanted while discarding the rest. Most stem cells are acquired through donation of left over embryos from IVF. IVF produces many more embryos than are actually used. If they are not donated for research purposes, the left over embryos are usually discarded, or, upon the wish of the parent, frozen to be thawed out later for possible use. However, in either of these instances, all or the majority of the embryos are lost as survival after cryopreservation and subsequent thawing is minimal (RT.org, 2004).
Embryonic stem cells are isolated from the blastocsyst by transferring the inner cell mass to a Petri dish, which is typically coated with mouse embryonic skin cells as a feeder layer for the stem cells to attach. These cells are allowed to proliferate until they fill the dish at which point some are removed and plated onto another plate to continue the proliferation. The original small clump of cells eventually yields millions of embryonic stem cells (NIH, 2001). Since these cells are not exposed to the usual chemical signals of a growing embryo in situ, these millions of cells have not differentiated yet contain the potential to differentiate into any of the 220 cell types of humans (RT.org, 2006), in other words they are pluripotent. Scientists have discovered several "recipes" for inducing differentiation into a few of these cell types. However, as long as they are grown under specific conditions they will not differentiate and result in the creation of an immortal cell line (NIH, 2001).
Adult stem cells are cells similar to embryonic stem cells but that reside in, and can be collected from, adults. These undifferentiated cells are found among differentiated cells in tissue or organ and differentiated to produce the specialized cell types of that tissue or organ. They have so far been identified in brain, bone marrow, peripheral blood, blood vessels, skeletal muscles, epithelia tissue, cornea and retina, dental pulp of the tooth, liver and pancreas. Their role is to maintain and repair the tissue in which they reside (NIH, Stem Cell Basics, 2006). Because of this they are not considered pluripotent as are embryonic stem cells, instead they are unipotent. However, recent research has shown that certain adult stem cells may be induced to differentiate into other types of cells, though again their differentiation is limited. For example, Hematopoietic cells in the bone marrow may differentiate into three major types of brain cells and bone marrow stromal cells may differentiate into cardiac and skeletal muscle cells besides their normal differentiated cell types (NIH, 2001). It is the trait of only being unipotent vs. pluripotent that researchers are primarily focusing on embryonic stem cells for the basis of their research, since they currently show the most potential in therapeutic use.
The uses for stem cells in treatment of disease have continued to increase as research pushes forward. The uses under current research include diabetes, heart disease, neural diseases such as Alzheimer's and Parkinson's, therapy of spinal injury and even the growth of new organs. The possible use of stem cells in each of these areas will be looked at more in depth.
Diabetes mellitus is a disorder characterized by chronic hyperglycemia with instability of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion, insulin action or both. Untreated, diabetes mellitus can lead to liver failure from nephropathy, complications of retinopathy with potential blindness, and autonomic dysfunction. People with diabetes are also at higher risk for cardiovascular, peripheral vascular and cerebrovascular disease (WHO, 1999). There are two types of diabetes. Type I is the result of the loss of beta cell function in the pancreas and absolute insulin deficiency due to the autoimmune-mediated destruction of beta cells. Type II diabetes is the result of impaired ability of the tissues to use insulin accompanied by a lack of insulin or impaired insulin release in relation to blood glucose levels (Porth, 2005 p. 994-997). It is estimated by the World Health Organization that approximately 300 million people suffer from diabetes world wide (Noguchi, 2006).
The typical treatment for diabetes is through intensive insulin therapy. Despite this treatment, however, most patients are unable to maintain normal blood glucose levels at all times. Over the last few decades there have been great successes with either total or partial transplant of pancreatic tissue. After a year, 83% of those who undergo a whole-organ pancreas transplant are symptom free (NIH, 2001). One study showed 500 diabetics undergoing transplant of insulin producing cells to cure their disease. However, the benefits of this were not lasting (Noguchi, 2006). This has led to research of stem cells to replace insulin producing cells.
There are several sources for replacement of insulin producing beta cells that are being investigated. First, studies using adult stem cells, collected from the lining of the pancreatic duct have proven promising. Ductal cells isolated from adult pancreatic tissue when cultured could be induced to differentiate into clusters of both ductal and endocrine cells and over several weeks began to produce low levels of insulin when exposed to low levels of glucose. This means cells from a diabetic could be cultured and implanted, giving the patient back their own cells. However, with Type I diabetes the autoimmune destruction would remain a problem for the transplanted cells. Research with embryonic stem cells could avoid this problem. As with adult stem cells, research has found that embryonic stem cells can be induced to form insulin-secreting structures. Embryonic stem cells though, have the potential to be engineered to express the appropriate genes that would reduce detection by the immune system, thereby making them more useful in Type I diabetes (NIH, 2001).
Heart disease is another area of research. Each year, nearly 1.1 million Americans suffer from a myocardial infarction, or heart attack. The affects of a heart attack can be devastating, resulting in the death of cardiomyocytes. The death of cardiomyocytes often leads to cardiac remodeling where the remaining heart muscle cells enlarge to compensate for the loss in heart function. Further complications of a heart attack result in congestive heart failure. The larger the infarct, the greater the chance for heart failure (Chande 2001) with fully half of those who are diagnosed with congestive heart failure dying within five years (NIH, 2001).
Stem cells have been shown to be able to help regenerate the tissue of the heart that has died following a heart attack. In one study researchers isolated bone-marrow stem cells and transplanted them into the hearts of mice that had induction of a myocardial infarction. Over a short amount of time these new cells migrated to the damaged area and formed heart muscle cells. Cells from bone marrow with characteristics of angioblasts (cells that differentiate into new blood vessels) were injected into rats a full two days after a myocardial infarction and once again found that they migrated to the damaged region and differentiated into new blood vessels. "The increase in oxygen and nutrients accompanying this new blood vessel formation in the damaged heart prevented the death of otherwise healthy myocardial cells and reduced cardiac remodeling" (Chande, 2001). The affects of this are believed to be permanent.
Even more hopeful research is being conducted in areas that were once thought impossible to treat, the nervous system. The nervous system is made up of nerve cells, called neurons, and glial cells which surround and support neurons. The loss of any of the cells that make up this system could have catastrophic effects on brain function ( NIH, Regenerative Medicine, 2006). Two diseases of this system are Alzheimer's and Parkinson's. Alzheimer's, is a result of cortical atrophy and loss of neurons that results in a steady decline in cognitive function. Symptoms include memory loss, personality changes, wandering, inability to communicate and seizures. Parkinson's disease is similar but is a degenerative disorder of the basil ganglia, which helps in the coordination of movement. This leads to a deficiency of dopamine and the result is uncontrollable tremors that can have a severely detrimental affect on a person's ability to perform simple tasks (Porth, 2005, p 1208-1212). The current treatment is a form of dopamine that can cross the blood brain barrier. This tends to work well initially, but slowly begins to lose its effectiveness, creating a constant battle for doctors. Thus, it is in Parkinson's disease that the most understood research is occurring.
Dopamine producing cells have been transplanted into the affected area before, the first effort being in the 1980s. However, this met with mixed results that were not long lasting and so the benefits did not outweigh the risk of the procedure itself. Early studies that involved the transplant of aborted fetal tissue into the affected area showed promising signs in younger and milder cases of Parkinson's. PET scans revealed that some of the transplanted cells had survived and matured in the same way as normal dopamine neurons. Because of this, researchers believe that embryonic stem cells may be an excellent source of dopamine neurons. Studies have shown that they have the ability to differentiate into both dopamine and serotonin neurons. Some of these studies have even shown engineered embryonic stem cells implanted in mice to correct Parkinson symptoms (NIH, Regenerative Medicine, 2006).
Treatment of other neural diseases could also benefit from the possibility of stem cell therapy. One of these is not so much a disease; spinal injury is a major area of research as well. Spinal cord trauma destroys many cell types. In many spinal injuries the cord is not severed and at least some of the signal carrying cells remain intact, however, they have lost their ability to transmit these signals because the insulating cells that surround them are lost (NIH, Regenerative Medicine, 2006). One recent success in treatment of this came from Korea where stem cells from umbilical cord blood were transplanted into a patient who suffered from a spinal cord injury that had prevented them from walking for the past 19 years. In just three weeks after the operation the patient was able to walk with the aid of a walker (Tae-gyu, 2004).
Treatment of disease is not the only possible use of stem cells. Currently, certain cell lines, like cancer cells are used to screen potential anti-tumor drugs. The availability of pluripotent cells could allow for testing of a wider range of drugs on a wider range of cell types (NIH, 2001). One such example of the possibilities this has is in a biotech firm called Cellular Dynamics International, started by James Thomson whose aim is to turn embryonic stem cells into human heart cells suitable for drug testing (Boyle, Alan, 2005). This would be beneficial in several ways. First of all, it could help eliminate the controversial issue of using animals to test drugs or other products. It could also serve as a more reliable model of what effect(s) potential drugs could have on human tissue, thus saving money and potentially many lives in the process (Tusin, 2001).
Finally, stem cells are also being investigated as a way to replenish tissue and possibly even organs that are damaged due to illness or degradation due to aging. New research is going into the development of the fine mesh scaffolding that is used to grow the cells on. Because the scaffolding is supposed to mimic the extracellular matrix, all of its properties are key to the cells growth and development. By altering the "expression" of different peptides on the scaffolding they can affect the behavior of the adhering cells. Even a slight change in the shape of the scaffolding can have profound effects. Investigator Patrick Stayton at the University of Washington is working on a project to bioengineer human-heart tissue. Their first goal is to develop a "patch" of tissue that could be used to repair and strengthen existing heart tissue. This research is looking promising as they have been able to coax the cells, through the proper methods, to produce fibrous strands similar to that of heart tissue that also form the specialized structures necessary to transmit the tension from contracting myofibrils from one cell to the next (McCarthy, 2000). This is all very preliminary but promising nonetheless.
With such amazing potential, what reason would be good enough to not pursue this line of research? This is where the controversy begins. The biggest problem that arises is from the use of embryonic stem cells. The controversy is brought on by the Orthodox Church. In a statement by Father Demetrios Demopulos Ph.D. of the Holy Trinity Greek Orthodox Church to the National Bioethics Advisory Comission in 2000, he clearly outlined the Orthodox Church's view of the embryo. The stance of the Orthodox Church follows the belief that the process towards which we as human beings are striving towards personhood and attainment of the likeness of God begins with the zygote. Their belief is that the embryo and the adult are both potential human persons just in different stages of development. The Church can therefore not condone procedures that threaten the viability and sanctity of life. This, they believe, is what research on embryonic stem cells does (the taking or sacrificing of a human life) and is therefore immoral. No exceptions can be made then for the use embryos left over from the process of in vitro fertilization as the discarding of those embryos is therefore immoral as well (National Bioethics Advisory Commision, 2000).
This is not the only opinion within the Church. In the same testimony, Ronald Cole-Turner, M.Div. Ph.D. a minister from the United Church of Christ stated that they have not come to the same conclusion about when life begins. His statement regarding the United Church of Christ's stance on embryonic stem cells was quite different. He upholds the same stance on doing what ever we possibly can in the pursuit of betterment of society through research that develops new medicinal technology and therefore states that embryonic research is not wrong. However, there are several stipulations that he makes in regards to the process. The primary stipulation is that embryos used are no more than 14 days of age, thus in the pre-embryo stage, the stage before the development of any early nervous system, for which they have no objection. The other stipulation is that the research be available for the common good. His main concern is for social justice, to not allow the therapy to be solely available for the wealthy at the expense of the poor and weak (National Bioethics Advisory Commision, 2000). Thus the concern for the greater good is more important than the fate of a several day old embryo.
These are just two viewpoints that are displayed in the church regarding stem cell research. It shows that there is no definitive stance within the church as a whole. Neither one condemns the use of adult stem cells but the Orthodox Church believes that life begins at fertilization and that use of an embryo at any stage is a sin. There are also non-religious arguments that favor the use of adult stem cells over embryonic stem cells. The main argument against embryonic stem cell use is the lack of knowledge of how to cultivate the cells compared with the much better understood way of cultivating adult stem cells. Embryonic stem cells can spontaneously differentiating into unwanted tissue types. It is this problem with embryonic stem cells that could lead to tumors (Clarke and Becker, 2006).
Is there any way to alleviate this controversy and still tap into the full benefits of stem cell research while alleviating the concern of the Church? As Father Demopulos stated in his testimony, the possibility of adult stem cells are greater than we had initially thought (National Bioethics Advisory Commision, 2000). However, the potential of embryonic stem cells remains high as well, just not as well understood. Alternatively, there are two other areas of research for stem cells that have not been as well researched and therefore deserve a mention. The first source of stem cells is from umbilical cord blood. Normally, the umbilical cord is simply discarded following birth. Recently, it has been discovered that it also harbors stem cells. Stem cells retrieved from umbilical cord blood have several advantages. First of all, they are easily obtained from the umbilical cord, unlike the surgical procedure necessary to obtain stem cells from the bone marrow of adults. Recipients of stem cells from cord blood also do not need to be as perfect a match as recipients of stem cells from bone marrow. Cord blood stem cells do not as easily induce graft versus host disease. This is because they have a muted immune reaction (March of Dimes, 2002). Finally, they appear to be more versatile than adult stem cells in their differentiation possibility, though still not as completely as embryonic stem cells (Coghlan, 2005). The other little known source for stem cells comes from amniotic fluid. Cells from amniotic fluid are already widely used in prenatal genetic testing. Recent observations of these cells suggest that they may represent a new source for the isolation of stem cells, exhibiting qualities such as fast proliferation and the ability to be cultured for extend lengths of time. Not much else is known about their potential for differentiation into various cell types so more research is needed (Prusa & Hengstsclager, 2002).
From the current research it is clear that embryonic stem cells have more potential since they are not limited in the types of tissue that they can differentiate into. However, embryonic stem cells could cause spontaneous growth and there are numerous therapies that can be derived with success from adult stem cells. Both of these types of cells have amazing potential that is yet unknown leading to the conclusion that research should continue on both. It will only be with further research that we will be able to fully understand and utilize that potential. That research comes at a cost that to some is unacceptable, since the use of embryonic stem cells to some is synonymous with taking a human life. However, even within the Church there is no clear stance on that idea. Because these cells hold such great potential in the therapy and possible curing of serious diseases or injuries, the benefit to society is much greater than the cost of the few embryos that are used to create the immortal cell lines. The fact is that the embryos used to begin these cell lines would be discarded anyway and otherwise do no good. Instead, they have the potential to help countless people and benefit the entire society. Thus, research should not be limited to adult stem cells but encompass all stem cell possibilities.
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