What is Wrong With Embryonic Stem Cell Research?

Introduction

Are conservatives more concerned about a tiny clump of cells than the suffering of their fellow human beings? Is embryonic stem cell research (ESCR) really the cure-all for countless diseases? If you haven't kept up with the science involved in ESCR, this paper will jump-start your knowledge of the issues.

Embryonic stem cell research is a hot topic that seems to pit anti-abortion conservatives against pro-abortion liberals. The conservatives claim that there are better alternatives to embryonic stem cells, while the liberals claim that conservatives are blocking research that will provide cures to many tragic diseases. Much of the rhetoric is designed to muddy the waters to invoke emotional responses of those within each camp. This paper is designed to break through sound-bites and go the heart of the matter - what are the scientific issues that impact the question of stem cell research.

Much of what is promoted as being news is actually an oversimplification of the issues. Many news articles about stem cell research never distinguish between the kind of stem cell research that is being promoted. For example, the media often reports of breakthrough treatment for patients without mentioning that, in all cases, the source of stem cells is adult tissues. We know this to be true, because embryonic stem cells have never been used in human patients, and won't likely be used in the near future (see reasons, below).

Stem cells are classified as being pluripotent or multipotent. Stem cells that are pluripotent are capable of forming virtually all of the possible tissue types found in human beings. These stem cells can only be found in a certain stage (a blastocyst) in human embryos. Multipotent stem cells are partially differentiated, so that they can form a limited number of tissue types. Multipotent stem cells can be found in the fetus, in umbilical cord blood, and numerous adult tissues. A summary of this information can be found in the Table 1.

A list of the sources of stem cells, along with their advantages and disadvantages can be found in Table 2.

Although the controversy of stem cell research is only recent, research first began in the 1960's. The primary source of early human stem cells was adult bone marrow, the tissue that makes red and white blood cells. Since scientists realized that bone marrow was a good source of stem cells, early transplants were initiated in the early 1970's to treat diseases that involved the immune system (genetic immunodeficiencies and cancers of the immune system). Bone marrow-derived stem cell therapy has been extremely successful, with dozens of diseases being treated and cured through the use of these adult stem cells. However, because the donor tissue type must be closely matched to the patient, finding a compatible donor can be problematic. If you haven't already done so, you should become part of the Bone Marrow Registry.

With the advent of animal cloning, scientists had thought that patient-specific human cloning might provide cures without the tissue incompatibility problems usually associated with transplants. Specific stem cells, developed using clones genetically identical to the patient, would integrate optimally into the patient's body. Although ideal in theory, problems associated with human cloning have been quite formidable. After many years of trying to produce human clones, a South Korean group claimed to have done so in 2004,2 followed by a claim that they had produced patient-specific clones. However, subsequent questions revealed that all the research was fraudulent. Contrary to the original claims, the researchers failed to produce even one clone after over 2,000 attempts. Although a number of labs are working on producing human clones, none have succeeded - even after several years of additional attempts. At a cost of $1,000-$2,000 just to produce each human egg,3 therapeutic cloning would easily cost hundreds of thousands of dollars, if not more, for each patient. Therefore, these kinds of therapies would only be available to the wealthy, assuming the technical difficulties will eventually be eliminated.

Three separate groups of researchers showed recently that normal skin cells can be reprogrammed to an embryonic state in mice.4 The fact that these iPS cells were pluripotent was proved by producing fetuses derived entirely from these transformed skin cells. Just five months after the mouse study was published, the feat was repeated by two separate laboratories using human skin cells.5 The ability to produce embryonic stem cell-like lines from individual patients removes the possibility of tissues rejection and avoids the high costs and moral problems associated with cloned embryos. Dr. Shinya Yamanaka, one of the study leaders later commented, "When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters... I thought, we cant keep destroying embryos for our research. There must be another way." The moral problem of destroying a human embryo encouraged Dr. Yamanaka to pursue a more ethical way to generate human stem cell lines. See the full report.

Stem cells have been promoted as a cure for numerous diseases in the popular press, although the reality of the science suggests otherwise. For example, claims that stem cells might cure Alzheimers disease are certainly untrue. According to Michael Shelanski, Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Columbia University Medical Center), I think the chance of doing repairs to Alzheimer's brains by putting in stem cells is small. Ronald D.G. McKay, National Institute of Neurological Disorders and Stroke says, To start with, people need a fairy tale.6 Stem cell research is widely promoted as a possible cure for type I and type II diabetes. However, these diseases involve the destruction of islet pancreatic cells by the patient's immune system. Even if tissue-compatible islet cells can be produced, transplanting them into a patient will be a very temporary cure, since the patient's immune system will attack the transplant in short order. So, a total cure for diabetes might have to involve a total immune compartment replacement (with its risks), in addition to an islet cell transplant. Parkinsons disease is another disease that is often mentioned as potentially curable through stem cell research. Proponents of ESCR cite studies in which embryonic stem cells produce dopamine in the brain of rats. However, only 50% of the rats had improvement of function and 25% developed brain tumors and died!7 A main problem for ESCR is that these stem cells spontaneously form tumors in virtually all studies that have been conducted to date. In addition, it seems that the number of dopamine-producing neurons declined over time, suggesting that the cure might be just temporary.8

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What is Wrong With Embryonic Stem Cell Research?

Embryonic stem cell – Science Daily

Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of a human embryo.

Embryonic stem cells are pluripotent, meaning they are able to grow (i.e. differentiate) into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm.

In other words, they can develop into each of the more than 200 cell types of the adult body as long as they are specified to do so.

Embryonic stem cells are distinguished by two distinctive properties: their pluripotency, and their ability to replicate indefinitely.

ES cells are pluripotent, that is, they are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm.

These include each of the more than 220 cell types in the adult body.

Pluripotency distinguishes embryonic stem cells from adult stem cells found in adults; while embryonic stem cells can generate all cell types in the body, adult stem cells are multipotent and can produce only a limited number of cell types.

Additionally, under defined conditions, embryonic stem cells are capable of propagating themselves indefinitely.

This allows embryonic stem cells to be employed as useful tools for both research and regenerative medicine, because they can produce limitless numbers of themselves for continued research or clinical use.

Because of their plasticity and potentially unlimited capacity for self-renewal, ES cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease.

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Embryonic stem cell - Science Daily

What are embryonic stem cells? [Stem Cell Information]

Introduction: What are stem cells, and why are they important? What are the unique properties of all stem cells? What are embryonic stem cells? What are adult stem cells? What are the similarities and differences between embryonic and adult stem cells? What are induced pluripotent stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized? Where can I get more information? A. What stages of early embryonic development are important for generating embryonic stem cells?

Embryonic stem cells, as their name suggests, are derived from embryos. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitroin an in vitro fertilization clinicand then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman's body.

Growing cells in the laboratory is known as cell culture. Human embryonic stem cells (hESCs) aregenerated by transferringcells from a preimplantation-stage embryointo a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. In the original protocol, the inner surface of the culture dish was coated with mouse embryonic skin cellsspecially treated so they will not divide. This coating layer of cells is called a feeder layer. The mouse cells in the bottom of the culture dish provide the cells a sticky surface to which they can attach. Also, the feeder cells release nutrients into the culture medium. Researchers have nowdevised ways to grow embryonic stem cells without mouse feeder cells. This is a significant scientific advance because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells.

The process of generating an embryonic stem cell line is somewhat inefficient, so lines are not produced each time cells from the preimplantation-stage embryo are placed into a culture dish. However, if the plated cells survive, divide and multiply enough to crowd the dish, they are removed gently and plated into several fresh culture dishes. The process of re-plating or subculturing the cells is repeated many times and for many months. Each cycle of subculturing the cells is referred to as a passage. Once the cell line is established, the original cells yield millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for for a prolonged period of time without differentiating, and are pluripotentare referred to as an embryonic stem cell line. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.

At various points during the process of generating embryonic stem cell lines, scientists test the cells to see whether they exhibit the fundamental properties that make them embryonic stem cells. This process is called characterization.

Scientists who study human embryonic stem cells have not yet agreed on a standard battery of tests that measure the cells' fundamental properties. However, laboratories that grow human embryonic stem cell lines use several kinds of tests, including:

As long as the embryonic stem cells in culture are grown under appropriate conditions, they can remain undifferentiated (unspecialized). But if cells are allowed to clump together to form embryoid bodies, they begin to differentiate spontaneously. They can form muscle cells, nerve cells, and many other cell types. Although spontaneous differentiation is a good indication that a culture of embryonic stem cells is healthy, it is not an efficient way to produce cultures of specific cell types.

So, to generate cultures of specific types of differentiated cellsheart muscle cells, blood cells, or nerve cells, for examplescientists try to control the differentiation of embryonic stem cells. They change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by inserting specific genes. Through years of experimentation, scientists have established some basic protocols or "recipes" for the directed differentiation of embryonic stem cells into some specific cell types (Figure 1). (For additional examples of directed differentiation of embryonic stem cells, refer to the NIH stem cell report available at http://stemcells.nih.gov/info/scireport/pages/2006report.aspx.)

Figure 1. Directed differentiation of mouse embryonic stem cells. Click here for larger image. ( 2008 Terese Winslow)

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What are embryonic stem cells? [Stem Cell Information]

Stem Cell Research Article, Embryonic Cells Information …

In the beginning, one cell becomes two, and two become four. Being fruitful, they multiply into a ball of many cells, a shimmering sphere of human potential. Scientists have long dreamed of plucking those naive cells from a young human embryo and coaxing them to perform, in sterile isolation, the everyday miracle they perform in wombs: transforming into all the 200 or so kinds of cells that constitute a human body. Liver cells. Brain cells. Skin, bone, and nerve.

The dream is to launch a medical revolution in which ailing organs and tissues might be repairednot with crude mechanical devices like insulin pumps and titanium joints but with living, homegrown replacements. It would be the dawn of a new era of regenerative medicine, one of the holy grails of modern biology.

Revolutions, alas, are almost always messy. So when James Thomson, a soft-spoken scientist at the University of Wisconsin in Madison, reported in November 1998 that he had succeeded in removing cells from spare embryos at fertility clinics and establishing the world's first human embryonic stem cell line, he and other scientists got a lot more than they bargained for. It was the kind of discovery that under most circumstances would have blossomed into a major federal research enterprise. Instead the discovery was quickly engulfed in the turbulent waters of religion and politics. In church pews, congressional hearing rooms, and finally the Oval Office, people wanted to know: Where were the needed embryos going to come from, and how many would have to be destroyed to treat the millions of patients who might be helped? Before long, countries around the world were embroiled in the debate.

Most alarmed have been people who see embryos as fully vested, vulnerable members of society, and who decry the harvesting of cells from embryos as akin to cannibalism. They warn of a brave new world of "embryo farms" and "cloning mills" for the cultivation of human spare parts. And they argue that scientists can achieve the same results using adult stem cells immature cells found in bone marrow and other organs in adult human beings, as well as in umbilical cords normally discarded at birth.

Advocates counter that adult stem cells, useful as they may be for some diseases, have thus far proved incapable of producing the full range of cell types that embryonic stem cells can. They point out that fertility clinic freezers worldwide are bulging with thousands of unwanted embryos slated for disposal. Those embryos are each smaller than the period at the end of this sentence. They have no identifying features or hints of a nervous system. If parents agree to donate them, supporters say, it would be unethical not to do so in the quest to cure people of disease.

Few question the medical promise of embryonic stem cells. Consider the biggest United States killer of all: heart disease. Embryonic stem cells can be trained to grow into heart muscle cells that, even in a laboratory dish, clump together and pulse in spooky unison. And when those heart cells have been injected into mice and pigs with heart disease, they've filled in for injured or dead cells and sped recovery. Similar studies have suggested stem cells' potential for conditions such as diabetes and spinal cord injury.

Critics point to worrisome animal research showing that embryonic stem cells sometimes grow into tumors or morph into unwanted kinds of tissuespossibly forming, for example, dangerous bits of bone in those hearts they are supposedly repairing. But supporters respond that such problems are rare and a lot has recently been learned about how to prevent them.

The arguments go back and forth, but policymakers and governments aren't waiting for answers. Some countries, such as Germany, worried about a slippery slope toward unethical human experimentation, have already prohibited some types of stem cell research. Others, like the U.S., have imposed severe limits on government funding but have left the private sector to do what it wants. Still others, such as the U.K., China, Korea, and Singapore, have set out to become the epicenters of stem cell research, providing money as well as ethical oversight to encourage the field within carefully drawn bounds.

In such varied political climates, scientists around the globe are racing to see which techniques will produce treatments soonest. Their approaches vary, but on one point, all seem to agree: How humanity handles its control over the mysteries of embryo development will say a lot about who we are and what we're becoming.

For more than halfof his seven years, Cedric Seldon has been fighting leukemia. Now having run out of options, he is about to become a biomedical pioneerone of about 600 Americans last year to be treated with an umbilical cord blood transplant.

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Stem Cell Research Article, Embryonic Cells Information ...

Practical Problems with Embryonic Stem Cells

While some researchers still claim that embryonic stem cells (ESCs) offer the best hope for treating many debilitating diseases, there is now a great deal of evidence contrary to that theory. Use of stem cells obtained by destroying human embryos is not only unethical but presents many practical obstacles as well.

"Major roadblocks remain before human embryonic stem cells could be transplanted into humans to cure diseases or replace injured body parts, a research pioneer said Thursday night. University of Wisconsin scientist James Thomson said obstacles include learning how to grow the cells into all types of organs and tissue and then making sure cancer and other defects are not introduced during the transplantation. 'I don't want to sound too pessimistic because this is all doable, but it's going to be very hard,' Thomson told the Wisconsin Newspaper Association's annual convention at the Kalahari Resort in this Wisconsin Dells town. 'Ultimately, those transplation therapies should work but it's likely to take a long time.'....Thomson cautioned such breakthroughs are likely decades away."

-Associated Press reporter Ryan J. Foley "Stem cell pioneer warns of roadblocks before cures," San Jose Mercury News Online, posted on Feb. 8, 2007, http://www.mercurynews.com/mld/mercurynews/16656570.htm

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"Although embryonic stem cells have the broadest differentiation potential, their use for cellular therapeutics is excluded for several reasons: the uncontrollable development of teratomas in a syngeneic transplantation model, imprinting-related developmental abnormalities, and ethical issues."

-Gesine Kgler et al., "A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential," Journal of Experimental Medicine, Vol. 200, No. 2 (July 19, 2004), p. 123.

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From a major foundation promoting research in pancreatic islet cells and other avenues for curing juvenile diabetes:

"Is the use of embryonic stem cells close to being used to provide a supply of islet cells for transplantation into humans?

"No. The field of embryonic stem cells faces enormous hurtles to overcome before these cells can be used in humans. The two key challenges to overcome are making the stem cells differentiate into specific viable cells consistently, and controlling against unchecked cell division once transplanted. Solid data of stable, functioning islet cells from embryonic stems cells in animals has not been seen."

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Practical Problems with Embryonic Stem Cells