Stem cell

File:Embryonic stem cell 20x (U of W-M).jpg

Microscopic 20x view of a colony of undifferentiated human embryonic stems cells (Source: University of Wisconsin-Madison.)

Stem cells are primal, undifferentiated cells which have the potential to produce any kind of cell in the body. Medical researchers believe stem cells have the potential to change the face of human disease by being used to repair specific tissues or to grow organs.

Types

There are three types of stem cells: totipotent, pluripotent, and multipotent. A single totipotent stem cell can grow into an entire organism and even produce extra-embryonic tissues, blastomeres have such properties. Pluripotent stem cells cannot grow into a whole organism, but they can become cells derived from any of the three germ layers, this implies a wide range of cellular differentiation. Multipotent (also called unipotent) stem cells can only become particular types of cells: e.g. blood cells, or bone cells.

Stem cells are also categorized according to their source, as either adult or embryonic. Adult stem cells are indifferentiated cells found among diffenrentiated cells of a specific tissue, and are mostly multipotent cells. They are already being used in treatments for over one hundred diseases and conditions, while embryonic stem cell research is a less developed field and is considered by many researchers to have greater potential as the basis of treatments. Embryonic stem cells are cultured cells obtained from the inner mass cells of a blastocyst. Research with embryonic stem cells is controversial because it requires destruction of embryos, which to many people are human beings, meaning that destroying an embryo for any reason is morally unacceptable. On the other side of the issue, people point out that embryonic stem cells have the potential to cure most diseases (since they are pluripotent), and the embryos used would have been discarded by fertility clinics anyway.

Sources of stem cells

Cord blood stem cells

Blood from the placenta and umbilical cord that are left over after birth is a source of adult stem cells. Since 1988 these cord blood stem cells have been used to treat Gunther's disease, Hunter syndrome, Hurler syndrome, Acute lymphocytic leukaemia and many more problems occurring mostly in children. It is collected by removing the umbilical cord, cleansing it and withdrawing blood from the umbilical vein. This blood is then immediately analyzed for infectious agents and the tissue-type is determined. Cord blood is stored in liquid nitrogen for later use, when it is thawed and injected through a vein of the patient. This kind of treatment, where the stem cells are collected from another donor, is called allogeneic treatment. When the cells are collected from the same patient they will be used on, it is called autologous and when collected from identical individuals, it is referred to as syngeneic. Xenogeneic transfer of cells between different species is very underdeveloped and is said to have little research potential.

Adult stem cells

Stem cells can be found in all adult beings. Adult stem cells are undiferentiated cells that reproduce daily to provide certain specialized cells—for example 200 billion red blood cells are created each day in the body. Until recently it was thought that each of these cells could produce just one particular type of cell—this is called differentiation (see Morphogenesis). However in the past few years, evidence has been gathered of stem cells that can transform into several different forms. Bone marrow stem cells are known to be able to transform into liver, nerve, muscle and kidney cells.

Adult stem cells may be even more versatile than this. Researchers at the New York University School of Medicine have extracted stem cells from the bone-marrow of mice which they say are pluripotent. Turning one type of stem cell into another is called transdifferentiation.

In fact, useful sources of adult stem cells are being found in organs all over the body. Researchers at McGill University in Montreal have extracted stem cells from skin that are able to differentiate into many types of tissue, including neurons, smooth muscle cells and fat-cells. These were found in the dermis, the inner layer of the skin. These stem cells play a pivotal role in healing small cuts. Blood vessels, the dental pulp, the digestive epithelium, the retina, liver and even the brain are all said to contain stem cells.

A major advantage of adult stem cells is that, since they can be harvested from the patient, moral issues and inmunogenic rejection are averted. Adult stem cells have already successfully treated over one hundred diseases and conditions, while embryonic stem cell research hasn't yet generated any treatments. Opponents of embryonic stem cell research have thus argued that embryonic stem cell funding restrictions in the US are not significantly impeding the advancement of stem cell research, and that even without the ethical concerns regarding embryonic stem cells, limited public health funds should focus on extending adult stem cell research successes until embryonic stem cell research is concretely proven to be a viable field through privately funded research on animal embryonic stem cells.

There are, however, at least presently, limitations to using adult stem cells. Although many different kinds of multipotent stem cells have been identified, adult stem cells that could give rise to all cell and tissue types have not yet been found. Adult stem cells are often present in only minute quantities and can therefore be difficult to isolate and purify. There is also evidence that they may not have the same capacity to multiply as embryonic stem cells do. Finally, adult stem cells may contain more DNA abnormalities—caused by sunlight, toxins, and errors in making more DNA copies during the course of a lifetime. These potential weaknesses might limit the usefulness of adult stem cells in comparison with embryonic stem cells.

Embryonic stem cells

Stem cells which derived from inner mass cells of a blsatocyst (future embryo) are seen to have the most potential because of their pluripotent properties—they are able to grow into any of the 200 cell types in the body. Embryonic stem cells can be obtained from a cloned embryo, created by fusing a denucleated egg-cell with a patient's cell. The embryo produced is allowed to grow to the size of a few tens of cells, and stem cells are then extracted. Because they are obtained from a clone, they are genetically compatible with the patient.

Although believed to have the largest medical potential, they are also the most controversial type of stem cells, because their utilization involves the destruction of human embryos. Some people believe that these embryos are human beings, and therefore destroying them for any reason is effectively mass murder. This belief is also the basis for the Pro-life opposition to abortion. On the other side of the debate, one scientist was quoted as saying that embryos contain only a few tens of cells and "the smallest insect is far more human in every respect except potential" [1]. Another justification is that the blastocyst from which the stem cells are taken may still divide into two embryos making identical twins, or (in rare cases), merge with another fertilized zygote to create a chimera, and therefore the blatocyst can not yet be considered an individual life. Some scientists also defend the use of embryos, citing the medical benefits that may one day be possible to achieve with them and the fact that many would have been destroyed, regardless. Pro-life groups respond that it could be possible to achieve the same benefits from the use of adult stem cells—although some scientists have placed greater hope in embryonic stem cell research instead.

Another controversy in the use of embryonic stem cells is the use of therapeutic cloning. This involves the cloning of early embryos from which stem cells are harvested, providing a larger source of the cells. Some see this as a form of reproductive human cloning, which they think is dangerous, unethical and morally wrong in any form.

In May of 2003, researchers announced that they had successfully used embryonic stem cells to produce human egg cells. Spokespersons stated that these egg cells could be used in turn to produce new stem cells. If research and testing proved that artificially created egg cells could be a viable source for embryonic stem cells, they noted, then this would remove the necessity of harvesting human embryos. Thus, the controversy over donating human egg cells and embryos would be largely dismissed, except that an embryo is required to start each cycle.

Current treatments

For over 30 years, bone marrow stem cells have been used to treat cancer patients with conditions such as leukemia and lymphoma. During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents not only kill the leukemia or neoplastic cells, but also the stem cells needed to replace the killed cells as a patient recovers. However, if the stem cells are removed before chemotherapy, and then reinjected after treatment is terminated, the stem cells in the bone marrow produce large amounts of red and white blood cells, to keep the body healthy and to help fight infections.

Since the 1980s stem cells have been taken from the blood instead of the bone-marrow, making the procedure safer for older people. Although normally scarce, the number of peripheral blood cells can be increased by a course of drugs, which release the stem cells from the bone-marrow. These are removed before chemotherapy, which kills most of them, and are re-injected afterwards.

Adult stem cells have been successfully used to treat paralysis due to spinal cord injuries, Parkinson's disease and other illnesses.

Potential treatments

Theoretically, virtually any disease could in time be treated by stem cells.

Research injecting neural (adult) stem cells into the brains of rats can be astonishingly successful in treating cancerous tumors. With traditional techniques brain cancer is almost impossible to treat because it spreads so rapidly. Researchers at the Harvard Medical School injected cells genetically engineered to convert a separately injected non-toxic substance into a cancer-killing agent. Within days the cells had migrated into the cancerous area and the injected substance was able to reduce tumor mass by 80 percent.

Stem cells are also apparently able to repair muscle damaged after heart attacks. Heart attacks are due to the coronary artery being blocked, starving tissue of oxygen and nutrients. Days after the attack is over, the cells try to remodel themselves in order to become able to pump harder. However, because of the decreased blood flow this attempt is futile and results in even more muscle cells weakening and dying. Researchers at Columbia-Presbyterian found that injecting bone-marrow stem cells into mice which had had heart attacks induced resulted in an improvement of 33 percent in the functioning of the heart. The damaged tissue had regrown by 68 percent. Clinical trials in humans are hoped for by 2003.

In the same way that organs can be transplanted from cadavers, researchers at the Salk Institute in California have found that these could be used as a source of stem cells as well. Taking stem cells from the brains of corpses they were able to coax them into dividing into valuable neurons. However, whether they will function correctly when used in treatment has not yet been determined.

Hair follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treating baldness through hair multiplication within three or four years (as of Nov. 2004). This treatment is expected to initially work through taking stem cells from existing follicles, multiplying them in cultures, and implanting the new follicles into the scalp. Later treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which respond to these signals by regenerating and once again making healthy hair. Web MD article

Type 1 Juvenile Diabetes could be cured with stem cells in the future.

Human hearts repaired using patient's own stem cells

Working with critically ill heart patients, researchers in Vienna have successfully used Mesenchymal stem cells to regenerate healthy new heart tissue. The stem cells were harvested from the patient's own bone marrow and injected into the ventricle. The heart is stopped for approximately two minutes to allow the stem cells to attach to the existing heart tissue. The patient is only under local anesthesia so that the surgeons can monitor how the lack of cerebral oxygen is affecting the patient. The heart is then restarted and incisions closed. The procedure is minimally invasive, as far as heart surgeories are concerned.

All of the patients that received the new treatment experienced repaired scar tissue and most had nearly complete return of proper heart function. As stated previously in the article, autologous stem cell implants such as these could alleviate legal and moral issues revolving around stem cell therapies.

Legal situation

Due to the controversy surrounding embryonic stem cells, on November 9, 2001 the U.S. National Institutes of Health announced a list of 72 approved human embryonic cell lines which researchers are to be allowed to work with. However, only 22 of these are available for distribution, due to isolates that failed to recover from cryopreservation and other reasons. Additionally, many of these lines are contaminated with mouse feeder cells, which may block FDA approval of techniques developed using these lines. Many scientists are also concerned with the quality of these lines; many are thought to be derivations of a single line and not independent lines, and many others have not been fully developed and characterized.

In the United Kingdom, the law states that a license may be issued to enable embryos to be created or used for research for the following purposes: (a) promoting advances in the treatment of infertility, (b) increasing knowledge about the causes of congenital disease, (c) increasing knowledge about the causes of miscarriages, (d) developing more effective techniques of contraception, or (e) developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation, (f) increasing knowledge about the development of embryos; (g) increasing knowledge about serious disease, or (h) enabling any such knowledge to be applied in developing treatments for serious disease. (Human Fertilisation and Embryology Act 1990 as amended by the Human Fertilisation and Embryology (Research Purposes) Regulations 2001).

Controversy over ethical implications

Some ethicists, philosophers, theologians and clergy are very concerned with the ethical implications of embryonic stem cell research. In the U.S. many Fundamentalist and Catholic Christian groups have come out strongly against embryonic stem cell research as they view it as a form of abortion, which they see as murder (many of those opposing embryonic stem cell research advocate adult stem cell research as an alternative [2]).

However, some proponents of research point out that fertility clinics routinely destroy thousands of embryos and have not been similarly protested against, and question the motivation of opponents of research [3]. Proponents also point out that embryos used for stem cell research would normally be discarded or kept frozen indefinitely if not used in research. Many Jewish groups are supportive of embryonic research, as they do not view an early stage embryo as a human being. Many Humanists, Unitarian Universalists, and many Muslim clerics have also come out in favor of stem cell research.

US President George W. Bush announced his executive decision on August 9, 2001, after consulting with "scientists, scholars, bioethicists, religious leaders, doctors, researchers, members of Congress, [his] Cabinet, and [his] friends" and reading "heartfelt letters from many Americans," to prohibit the use of federal funding to work with embryonic cell lines created after that date. In 2002, President Bush appointed a Council on Bioethics composed of 18 doctors, legal and ethical scholars, scientists and a journalist. In February, 2004 Bush removed from the council professors of ethics William May and biologist Elizabeth Blackburn. These two outspoken advocates of stem cell research were replaced with Benjamin Carson, Diana Schaub and Peter Lawler, all three of whom have expressed more conservative views on biotechnology.

The Bush administration's decision does not prohibit private embryonic stem cell research, but so far most pharmaceutical companies and biotechnology companies have expressed little interest because they consider therapies based on cells, which might have to be tailored to each patient, to be less profitable than one-size-fits-all drugs. Others are reluctant to enter the market because they fear government bans, perventing them from capitalizing on the reseach.

As a result of the ban, the US, normally a global leader in science, has fallen behind other countries in embryonic stem cell research, including South Korea (successfully cloning human embryos in early 2004 and extracting stem cells from them) and the United Kingdom (creating the world's first stem cell bank in May 2004). Because other countries have moved forward with their stem cell research programs, some in the US have questioned the Bush Administration's ban.

In April 2004, 206 members of Congress, including many moderate republicans, and some other prominent public figures signed a letter urging President Bush to relax the policy. The 2004 Democratic presidential candidate, John Kerry, had promised to support all types of stem cell research if elected President, but his defeat in the U.S. presidential election, 2004 meant that embryonic stem cell research in the US would occur mainly in California, due to the passing of California's Prop. 71.

California Proposition 71 (2004)

On November 2, 2004, California passed by 59% to 41% a ballot initiative (California Proposition 71 (2004)) to create a $3 billion state taxpayer-funded institute for embryonic stem cell research, the California Institute for Regenerative Medicine. The institute is claimed to be the world's largest single backer of research in stem cells, having the potential to make the state a global leader in the pioneering field and to invigorate the field, which has been hampered in the US by federal funding restrictions. It is expected to draw many of the US's most talented stem cell researchers to the state.

The initiative had received contributions from figures such as Bill Gates, venture capitalist John Doerr (an early backer of Internet search engine Google), and eBay founder Pierre Omidyar, as well as actors Michael J. Fox and the late Christopher Reeve, both suffering from conditions that might one day be helped by stem cell research. It was also backed by California governor Arnold Schwarzenegger, a moderate republican. Opposition felt strongly about the issue and came from an unusual coalition of groups, including individuals from the far-right all the way to the far-left, including women's health groups and some Green Party groups [4]. Some proponents believe other US states may follow with similar propositions, creating a state-by-state approach that sidesteps the Bush administration's federal funding restrictions.

Following the passing of the proposition, Robert Klein, co-chair of the Yes on 71 campaign, summarized the feelings of some proponents, saying "there is no doubt in my mind that the mission Californians accepted today is a critical first step in changing the face of human suffering forever." With 41% of the state opposed to the proposition, however, it remains controversial.

The California Prop 71 Stem cell oversight committee is consisted of several elected officials and four UC Chancellors, including UC Berkeley's Chancellor Robert J. Birgeneau.

19 days following the passing of California's Prop. 71, leading state officials from Wisconsin, New Jersey, and Illinois have announced plans of similar state funding initiatives in order to prevent their top leading biotech researchers from flocking to California.

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