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Stem cell



Stem cells are primal, undifferentiated cells which have the unique potential to produce any kind of cell in the body. Many medical researchers believe stem cells have the potential to revolutionize medicine, enabling doctors to repair specific tissues or to grow organs.

Contents

Types

There are three types of stem cells:

  • A single totipotent stem cell can grow into an entire organism and even produce extra-embryonic tissues. Blastomeres have this property.
  • Pluripotent stem cells cannot grow into a whole organism, but they are able to differentiate into cells derived from any of the three germ layers.
  • Multipotent (also called unipotent) stem cells can only become some 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 undifferentiated cells found among differentiated cells of a specific tissue and are mostly multipotent cells. They are already being used in treatments for over one hundred diseases and conditions. They are more accurately called somatic (Greek σωμα sōma = body) stem cells, because they need not come from adults but can also come from children or umbilical cords.
Embryonic stem cells are cultured cells obtained from the inner mass cells of a blastocyst. Embryonic stem cell research is still in the basic research phase. Research with embryonic stem cells derived from humans is controversial because, in order to start a stem cell 'line' or lineage, it requires the destruction of a blastocyst (an embryo that has not yet grown beyond 150 cells), which some people believe to be human beings. (See below: embryonic stem cell ethical debate)

Sources of stem cells

Cord blood stem cells

Blood from the placenta and umbilical cord that are left over after birth is one 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. The cord blood is processed and depleted of red blood cells before being stored in liquid nitrogen for later use, at which point it is thawed, washed of the cryoprotectant, 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 on whom they will be used, 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.

Researchers in South Korea announced in November 2004 that they had successfully used multipotent cord blood (adult) stem cell treatments to enable a paralyzed woman to walk with the aid of a walker. This was achieved by isolating the stem cells from the umbilical cord blood and injecting the cells into the damaged part of the woman's spinal cord. Work was done by Chosun University professor Song Chang-hun, Seoul National University professor Kang Kyung-susn, and the Seoul Cord Blood Bank.[1] [2] [3] [4]

Adult stem cells

Stem cells can be found in all adult and young adult beings. Adult stem cells are undifferentiated cells that reproduce daily to provide certain specialized cells—for example 200 billion red blood cells are created each day in the body from hemopoietic stem cells. 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 stromal stem cells are known to be able to transform into liver, nerve, muscle, hair follicle 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.

Adipose derived adult stem (ADAS) cells have also been isolated from fat, e.g. from liposuction. This source of cells seems to be similar in many ways to Mesenchymal stem cells (MSCs) derived from bone marrow, except that it is possible to isolate many more cells from fat. These cells have been shown to differentiate into bone, fat, muscle, cartilage, and neurons. These cells have been recently used to successfully repair a large cranial defect in a human patient [5].

Olfactory adult stem cells have been successfully grown by Prof. Alan Mackay-Sim,[6] deputy director of Griffith University’s new Institute for Cellular and Molecular Therapies in Brisbane, Queensland, Australia. He was awarded Queenslander of the Year in 2003 for his work. His team successfully grew adult stem cells harvested from the human nose, and was published in the journal Developmental Dynamics. The Courier-Mail cited him as follows (22 March 2005, p. 4):

Adult stem cells isolated from the olfactory mucosa (cells linking the inside of the nose involved in the sense of smell) have the ability to develop into many different cell types if they are given the right chemical environment.
These adult olfactory stem cells appear to have the same ability as embryonic stem cells in giving rise to many different cell types but have the advantage that they can be obtained from all individuals, even older people who might be most in need to stem cell therapies. ...
Adult olfactory stem cells are readily obtained from the nose and relatively easy to grow and multiply in the lab. In a few weeks we can make plenty of cells for transplantation.

An advantage of adult stem cells is that, since they can be harvested from the patient, potential ethical issues and inmunogenic rejection are averted. 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 limited 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. However, there are a number of clinically proven adult stem cell successes.

Embryonic stem cells

Stem cells which derived from the inner mass cells of a blastocyst (an early embryo) have 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 blastocyst, created by fusing a denucleated egg cell with a patient's cell. The blastocyst 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. Aggregates of cells derived from embryonic stem cells are known as embryoid bodies .

The breakthrough in embryonic stem cell research came in November 1998 when a group led by James Thomson at the University of Wisconsin first developed a technique to isolate and grow the cells. Embryonic stem cell researchers are currently attempting to grow the cells beyond the first stages of cell development, to overcome difficulties in host rejection of implanted stem cells, and to control the multiplying of implanted embryonic stem cells, which otherwise multiply uncontrollably, producing cancer.

A major development in research came in May 2003, when researchers announced that they had successfully used embryonic stem cells to produce human egg cells. These egg cells could potentially be used in turn to produce new stem cells. If research and testing proves that artificially created egg cells could be a viable source for embryonic stem cells, they noted, then this would remove the necessity of starting a new embryonic stem cell line with the destruction of a blastocyst. Thus, the controversy over donating human egg cells and blastocysts could potentially be resolved, though a blastocyst would still be required to start each cycle.

The online edition of Nature Medicine published a study on January 23, 2005 which stated that the human embryonic stem cells available for federally funded research are contaminated with nonhuman molecules from the culture medium used to grow the cells, for example, mouse cells and other animal cells. The nonhuman cell-surface sialic acid can compromise the potential uses of the embryonic stem cells in humans--according to scientists at the University of California, San Diego[7].

A study was published in the Lancet Medical Journal on March 8, 2005 that detailed information about a new stem-cell line which was derived from human embryos under completely cell and serum free conditions. This event is significant because exposure of existing human embryonic stem-cell lines to live animal cells and serum risks contamination with pathogens that could lead to human health risks. After more than 6 months of undifferentiated proliferation, these cells retained the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem-cell lines. (Lancet Medical Journal)

Treatments

Current treatments

For over 30 years, bone marrow (adult) 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 also been successfully used to treat paralysis due to spinal cord injuries, Parkinson's disease and other illnesses.

Potential treatments

Cancer

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 adult stems cells genetically engineered to convert a separately injected non-toxic substance into a cancer-killing agent. Within days the adult stem cells had migrated into the cancerous area and the injected substance was able to reduce tumor mass by 80 percent.

Spinal cord

Embryonic stem cells switched to neurons

In Jan. 2005, using stem cells science made major progress in understanding the process of how mammalian stem cells differentiate to form specific types of brain cells. This could lead to new treatments and cures for diseases like Lou Gehrig's disease, muscular dystrophy, and spinal cord injuries.

Researchers at the University of Wisconsin-Madison coaxed human embryonic stem cells into becoming neural stem cells, then into the beginnings of motor neurons before finally differentiating into spinal motor neuron cells, the cell type that, in the human body, transmits messages from the brain to the spinal cord. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Researcher Su-Chun Zhang described the process as "you need to teach the [embryonic stem cells] to change step by step, where each step has different conditions and a strict window of time."

Transforming embryonic stem cells into motor neurons had eluded researchers for decades, until now. The next step will be to test if the newly generated neurons can communicate with other cells when transplanted into a living animal. The team will first test the neurons in chicken embryos. Lead researcher Su-Chun Zhang said their trial-and-error study helped them learn how motor neuron cells, which are key to the nervous system, develop in the first place.

Stem cell injection restores ability to walk

A team of Korean researchers reported on November 25, 2004, that they had transplanted multi-potent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and she can now walk on her own, with difficulty. The patient could not even stand up for the last 19 years. The team was co-headed by researchers at Chosun University, Seoul National University and the Seoul Cord Blood Bank (SCB). For the unprecedented clinical test, the scientists isolated adult stem cells from umbilical cord blood and then injected them into the damaged part of the spinal cord.

Using adult stem cells, the tests were able to avoid triggering a negative bodily reaction, which are common in other transplantations, according to Hoon Han, one of the researchers. "We don’t need a strict match between cord blood stem cell type and the immune system of a patient because the latter accepts the former pretty well thanks to its immaturity," Han said. [8]

Muscle damage

Adult 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, a form of adult 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.

Human hearts repaired using patient's own stem cells

Using the patient's own bone marrow derived stem cells, Dr. Amit Patel at the University of Pittsburgh, Mcgowan Institute of Regenerative Medicine MIRMhas shown a dramatic increase in ejection fraction for patients with congestive heart failure. Working with critically ill heart patients, researchers in Vienna have successfully used Mesenchymal stem cells to regenerate healthy new heart tissue. The adult 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 adult 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 surgeries 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.

Neurology

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 adult stem cells as well. Taking adult 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.

Blood supplies

For many years, researchers have hoped to develop red blood cells from stem cells. In December 2004, researchers at the University of Paris developed a way to produce large numbers of red blood cells. The three-stage process involves combining adult stem cells with another group of cells called stromal cells and then adding a growth factor to stimulate them. The study is outlined in Nature Biotechnology. The Paris University team, lead by Professor Luc Douay, devised a technique which involves three steps: 1. Take haematopoietic stem cells, which are known to evolve into blood cells and treat them with a liquid to make them proliferate, 2. Create an environment to mimic the conditions found in bone marrow by using stromal cells, which provide the structure inside bone marrow, and 3. Add a growth factor called erythropoietin, which provides a signal to the stem cells to begin the transformation into red blood cells. The stem cells can be autologous, which is the safest form of blood transfusion.

Baldness

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'/'hair cloning' 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 in turn respond to these signals by regenerating and once again making healthy hair. Hair Cloning Nears Reality as Baldness Cure (Web MD Nov. 2004)

Embryonic stem cell ethical debate

Blastocysts

A blastocyst is a stage of development of an embryo when it is around five days old and made up of about 100 cells. A blastocyst at the stage at which embryonic stem cells would be extracted is still young enough to be able to divide into two embryos, making identical twins, or in rare cases, merge with another blastocyst, even one of the opposite sex[1], to create a chimera, an individual comprised of populations of cells with two different sets of DNA. From the biological point of view, these points mean the blastocyst is not yet an individual. Blastocysts are an early developmental stage far from possessing a nervous system, and thus biologically speaking do not have feelings.

Some ethicists and religious figures are very concerned with the ethical implications of embryonic stem cell research. Some people believe that a human blastocyst is a human being with the same fundamental human rights. Some of these people thus oppose embryonic stem cell research because the start of each cell line involves the destruction of a blastocyst.

This view raises other issues, as the blastocysts involved in the research are left over from in vitro fertility therapy, and when not used in additional therapy or in embryonic stem cell research are destroyed or frozen indefinitely by the thousands[9]. To some, this does not address the concern that using doomed blastocysts in embryonic stem cell research is viewed as instrumentalizing a developing human being.

In the U.S., many Christian groups (such as Fundamentalists, Catholics, and Eastern Orthodox) believe that a human blastocyst is a human being and oppose embryonic stem cell research.

Others do not view a blastocyst as a human being, and may instead see opposition of stem cell research as unethical due to the suffering that new medical technologies could prevent. Many Jews, Muslims, Humanists, and Unitarian Universalists, as well as a significant number of mainstream Christians are supportive of embryonic stem cell research.

Another area in embryonic stem cells that can be of ethical concern is the use of therapeutic cloning. This involves using a blastocyst cloned from the patient so that the resulting stem cells are a genetic match. Some see this as being in a category of unnaturalness shared with reproductive human cloning, in which cloned blastocysts would be allowed to grow into embryos and eventually infants. [10]

Policy debate in the U.S.

In 1995, Congress passed the Dickey Amendment, prohibiting federal funding of research that involves the use of a human embryo. Privately funded research led to the breakthrough which made embryonic stem cell research possible in 1998, however, prompting the Clinton Administration to develop federal regulations for its funding. Preparations for this funding were completed in 2001. President George W. Bush announced, on August 11, 2001, that for the first time federal funds would be used to support research on human embryonic stem cells, but that funding would be limited to "existing (embryonic) stem cell lines where the life and death decision has already been made". President Bush also stated that the federal government would continue to support research involving stem cells from other sources, such as umbilical cord blood, placentas, and adult and animal tissues. Some felt the restrictions should have been stronger, while some scientists felt frustrated with the restrictions.

In 2002, President Bush appointed the Council on Bioethics, an advisory group composed of 18 doctors, legal and ethical scholars, scientists and a journalist. In February, 2004 Bush removed from the council two advocates of embryonic stem cell research, professor of ethics William May and biologist Elizabeth Blackburn. In their place, he appointed pediatric neurosurgeon Dr. Benjamin Carson, political scientist Dr. Diana Schaub, and professor of government Dr. Peter Lawler, all of whom have expressed a more cautionary view towards embryonic stem cell research.

The Bush administration's decision does not prohibit private embryonic stem cell research. Pharmaceutical companies and biotechnology companies initially 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. However, there are many start-up biotechs that are now entering the field. They include: StemCells Inc. and Aastrom Biosciences. Others are reluctant to enter the market because they fear government restrictions preventing them from capitalizing on the research. However, individual medical treatments are being financed by private research groups such as pharmaceutical and biotechnology companies. These are the groups that have financed all of the medical treatments outlined in this article.

As a result of the federal funding restrictions, embryonic stem cell research in the US is commonly acknowledged to have been hampered in comparison with other countries, such as South Korea, which successfully cloned human embryos in early 2004 and extracting embryonic stem cells from them. However, the leading stem cell researchers in South Korea have a developed a stem cell bank that only holds adult stem cells from individuals. The Seoul Cord Blood Bank (SCB) currently retains blood from about 45,000 umbilical cords, which are enough to cover all Koreans, amply demonstrating the immeasurable potential of new adult stem cell therapies, e.g., the spiral cord treatment outlined above. The United Kingdom created the world's first embryonic stem cell bank in May 2004. However, there are hundreds of private adult stem cell banks worldwide, e.g., cord blood banks. Because other countries have moved forward with their embryonic stem cell research programs, some in the US have questioned the funding restriction.

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, Senator John Kerry (D, MA), had promised to support all types of stem cell research if elected President. His defeat in the U.S. presidential election, 2004 means that embryonic stem cell research in the US will potentially develop at the state level, especially in California, due to the passing of California's Prop. 71. Some scientists are concerned that stem cell research has become a politicized issue instead of a scientific issue in the national mindset, and feel that the politicization distorts representation of the scientific issues.

Adult stem cells have successfully treated over one hundred diseases and conditions. Opponents of embryonic stem cell research have thus argued that embryonic stem cell funding restrictions in the US are not significantly impeding the overall advancement of stem cell research, and that even without the ethical concerns regarding embryonic stem cells, public health funds should focus on extending adult stem cell research successes.

Emerging US state-by-state approach

California voted in Nov. 2004 to create a $3 billion state taxpayer-funded institute for stem cell research, the California Institute for Regenerative Medicine. Providing $300 million a year, the institute is claimed to be the world's largest single backer of research in stem cells, and could potentially increase substantially the pace of embryonic stem cell research.

Several states, in some cases wary of a national migration of biotech researchers to California, have shown interest in providing their own funding support of embryonic and adult stem cell research. These states include Pennsylvania, New York, New Jersey, Florida, Texas [11][12], Illinois, Massachusetts, Wisconsin, Washington, and New Hampshire.

Other states, presently have, or have shown interest in, additional restrictions or even complete bans on embryonic stem cell research. These states include Arkansas, Iowa, Louisiana, Michigan, Nebraska, North Dakota, South Dakota, Virginia, Kansas, and Missouri,

International situation

Due to the controversy surrounding embryonic stem cells, many nations around the world have passed legislation regulating research.

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:

  1. promoting advances in the treatment of infertility,
  2. increasing knowledge about the causes of congenital disease,
  3. increasing knowledge about the causes of miscarriages,
  4. developing more effective techniques of contraception, or
  5. developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation,
  6. increasing knowledge about the development of embryos;
  7. increasing knowledge about serious disease, or
  8. 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).

The nations spending the most on stem cell research [13] include the US, the United Kingdom, South Korea, China, Australia, Israel, Singapore, Argentina, Uruguay and Sweden. European nations that permit stem cell research also include Switzerland [14], Finland, Greece and the Netherlands. The UK allows the creation of human embryos for stem cell procurement. Countries with regulations allowing cloning for medical research include the UK, Belgium, Singapore and Japan. Recently Brazil has approved a law allowing the use of stem cells into researches.

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