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stem cell


n.

An unspecialized cell that gives rise to a specific specialized cell, such as a blood cell.


 
 
Sci-Tech Encyclopedia: Stem cells

Cells that have the ability to self-replicate and give rise to specialized cells. Stem cells can be found at different stages of fetal development and are present in a wide range of adult tissues. Many of the terms used to distinguish stem cells are based on their origins and the cell types of their progeny.

There are three basic types of stem cells. Totipotent stem cells, meaning their potential is total, have the capacity to give rise to every cell type of the body and to form an entire organism. Pluripotent stem cells, such as embryonic stem cells, are capable of generating virtually all cell types of the body but are unable to form a functioning organism. Multipotent stem cells can give rise only to a limited number of cell types. For example, adult stem cells, also called organ- or tissue-specific stem cells, are multipotent stem cells found in specialized organs and tissues after birth. Their primary function is to replenish cells lost from normal turnover or disease in the specific organs and tissues in which they are found.

Totipotent stem cells occur at the earliest stage of embryonic development. The union of sperm and egg creates a single totipotent cell. This cell divides into identical cells in the first hours after fertilization. All these cells have the potential to develop into a fetus when they are placed into the uterus. The first differentiation of totipotent cells forms a hollow sphere of cells called the blastocyst, which has an outer layer of cells and an inner cell mass inside the sphere. The outer layer of cells will form the placenta and other supporting tissues during fetal development, whereas cells of the inner cell mass go on to form all three primary germ layers: ectoderm, mesoderm, and endoderm. The three germ layers are the embryonic source of all types of cells and tissues of the body. Embryonic stem cells are derived from the inner cell mass of the blastocyst. They retain the capacity to give rise to cells of all three germ layers. However, embryonic stem cells cannot form a complete organism because they are unable to generate the entire spectrum of cells and structures required for fetal development. Thus, embryonic stem cells are pluripotent, not totipotent, stem cells.

Embryonic germ (EG) cells differ from embryonic stem cells in the tissue sources from which they are derived, but appear to be similar to embryonic stem cells in their pluripotency. Human embryonic germ cell lines are established from the cultures of the primordial germ cells obtained from the gonadal ridge of late-stage embryos, a specific part that normally develops into the testes or the ovaries. Embryonic germ cells in culture, like cultured embryonic stem cells, form embryoid bodies, which are dense, multilayered cell aggregates consisting of partially differentiated cells. The embryoid body-derived cells have high growth potential. The cell lines generated from cultures of the embryoid body cells can give rise to cells of all three embryonic germ layers, indicating that embryonic germ cells may represent another source of pluripotent stem cells.

Much of the knowledge about embryonic development and stem cells has been accumulated from basic research on mouse embryonic stem cells. Since 1998, however, research teams have succeeded in growing human embryonic stem cells in culture. Human embryonic stem cell lines have been established from the inner cell mass of human blastocysts that were produced through in vitro fertilization procedures. The techniques for growing human embryonic stem cells are similar to those used for growth of mouse embryonic stem cells. However, human embryonic stem cells must be grown on a mouse embryonic fibroblast feeder layer or in media conditioned by mouse embryonic fibroblasts. Human embryonic stem cell lines can be maintained in culture to generate indefinite numbers of identical stem cells for research. As with mouse embryonic stem cells, culture conditions have been designed to direct differentiation into specific cell types (for example, neural and hematopoietic cells).

Adult stem cells occur in mature tissues. Like all stem cells, adult stem cells can self-replicate. Their ability to self-renew can last throughout the lifetime of individual organisms. But unlike embryonic stem cells, it is usually difficult to expand adult stem cells in culture. Adult stem cells reside in specific organs and tissues, but account for a very small number of the cells in tissues. They are responsible for maintaining a stable state of the specialized tissues. To replace lost cells, stem cells typically generate intermediate cells called precursor or progenitor cells, which are no longer capable of self-renewal. However, they continue undergoing cell divisions, coupled with maturation, to yield fully specialized cells. Such stem cells have been identified in many types of adult tissues, including bone marrow, blood, skin, gastrointestinal tract, dental pulp, retina of the eye, skeletal muscle, liver, pancreas, and brain. Adult stem cells are usually designated according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited to one or more lineages of specialized cells. However, a special multipotent stem cell that can be found in bone marrow, called the mesenchymal stem cell, can produce all cell types of bone, cartilage, fat, blood, and connective tissues.

Blood stem cells, or hematopoietic stem cells, are the most studied type of adult stem cells. The concept of hematopoietic stem cells is not new, since it has been long realized that mature blood cells are constantly lost and destroyed. Billions of new blood cells are produced each day to make up the loss. This process of blood cell generation called hematopoiesis, occurs largely in the bone marrow. Another emerging source of blood stem cells is human umbilical cord blood. Similar to bone marrow, umbilical cord blood can be used as a source material of stem cells for transplant therapy. However, because of the limited number of stem cells in umbilical cord blood, most of the procedures are performed for young children of relatively low body weight.

Neural stem cells, the multipotent stem cells that generate nerve cells, are a new focus in stem cell research. Active cellular turnover does not occur in the adult nervous system as it does in renewing tissues such as blood or skin. Because of this observation, it had been a dogma that the adult brain and spinal cord were unable to regenerate new nerve cells. However, since the early 1990s, neural stem cells have been isolated from the adult brain as well as fetal brain tissues. Stem cells in the adult brain are found in the areas called the subventricular zone and the ventricle zone. Another location of brain stem cells occurs in the hippocampus, a special structure of the cerebral cortex related to memory function. Stem cells isolated from these areas are able to divide and to give rise to nerve cells (neurons) and neuron-supporting cell types in culture.

Stem cell plasticity refers to the phenomenon of adult stem cells from one tissue generating the specialized cells of another tissue. The long-standing concept of adult organ-specific stem cells is that they are restricted to producing the cell types of their specific tissues. However, a series of studies have challenged the concept of tissue restriction of adult stem cells. Although the stem cells appear able to cross their tissue-specific boundaries, crossing occurs generally at a low frequency and mostly only under conditions of host organ damage. The finding of stem cell plasticity carries significant implications for potential cell therapy. For example, if differentiation can be redirected, stem cells of abundant source and easy access, such as blood stem cells in bone marrow or umbilical cord blood, could be used to substitute stem cells in tissues that are difficult to isolate, such as heart and nervous system tissue. See also Cell differentiation; Embryology; Embryonic differentiation; Germ layers; Hematopoiesis; Regeneration (biology); Transplantation biology.

 
World of the Body: stem cells

Stem cells are ‘uncommitted’ cells, capable of dividing to make more stem cells, or, under appropriate conditions, to produce the kinds of specialized cells that make up the tissues and organs of the body.

A newly fertilized egg is the ultimate stem cell. It is totipotent - capable of generating all the different types of cells found in the body, and also the fetal part of the placenta and supporting tissues. The fertilized egg splits into two, and those into four, and so on. For the first few divisions, up to at least the 8-cell stage, all the cells of the tiny embryo are totipotent stem cells. Indeed, if these early cells separate, they can each continue to develop, making identical twins, triplets, quadruplets, etc.

About four days after fertilization, the route to commitment starts. Some cells form an outer layer, which becomes part of the placenta, while others make the inner mass, which is the beginning of the true embryo. Initially this consists entirely of pluripotent stem cells, which cannot give rise to placental tissue but can make any component of the fetus itself. As the embryo grows, and the parts of the body start to emerge, the individual stem cells within each future organ or tissue become further specialized so as to be capable of producing only a certain range of possible final cell types. These stem cells are then called multipotent. At a certain stage in the development of each ‘family tree’ of cells, one or both of the daughter cells produced by the division of a stem cell becomes ‘committed’, that is, incapable of further division. These committed daughters continue to differentiate and become the normal functional cells of the heart, skin, brain, kidney, and other organs.

Adult animals still have some multipotent stem cells, especially in tissues such as skin and blood, in which cells last only a short time and have to be replaced. Indeed, even in the adult brain, previously thought to be incapable of making new nerve cells, there are populations of stem cells, which are constantly producing relatively small numbers of new neurons.

We now stand at the threshold of a potential revolution in medical treatment for diseases and disorders in which organs stop working properly. At present, some such conditions, such as heart, kidney and liver disease, can be treated by transplantation of a replacement organ from another person. But demand for donor organs is far outstripping supply, and the failure rate of such surgery is quite high, mainly because of the problem of rejection. Many other disorders, such as stroke, diabetes and Alzheimer's disease, cannot presently be treated by transplantation. The great hope is that suitable stem cells, produced in large quantities through cell culture methods and injected into failing tissues and organs, will produce fresh, replacement cells to take over from lost or damaged ones.

Stem cells for such replacement therapy could be produced in a number of different ways. Ultimately, it might be possible to make them with the kind of methods used to produce the first cloned mammal, Dolly the sheep. An ordinary specialized adult cell from the patient could be used to produce a totipotent stem cell by removing the nucleus (with the DNA-containing chromosomes), and inserting it into a human egg from which the nucleus has been removed. But there are many problems with this approach, not least the fact that adult cells may have accumulated genetic errors, which will be transmitted to the stem cells produced. Everyone agrees that formidable technical obstacles must be overcome before the cloning of stem cells from adult cells becomes safe. There is also concern that the development of methods for therapeutic cloning would inevitably lead to the production of whole human beings, who, like Dolly, are genetic replicas of an adult. At present, the vast majority of scientists and clinicians, not to mention ethicists and politicians, are opposed to such reproductive cloning, but it must be said that resistance may decrease if the techniques involved can be made more reliable.

In principle, some of the patient's own stem cells could be harvested (most likely from bone marrow or certain parts of the brain), multi-plied in culture and injected into a diseased or damaged region to produce new cells. Stem cells derived from the patient's own body would have the great advantage that they would not be rejected. This approach has already been successful in experimental animals, with stem cells from bone marrow used to replace damaged heart muscle. It may soon be used in humans to treat heart disease, diabetes, and other such diseases. However, it would not be appropriate for the replacement of tissues that are diseased because of a genetic disorder (such as Huntington's disease or cystic fibrosis), since stem cells from the patient would have the same genetic mistake in their DNA. This strategy would also be inappropriate in acute conditions, demanding immediate treatment, because of the time needed for stem cells to multiply in culture.

The most immediately promising strategy is to isolate pluripotent stem cells from human embryos just a few days after fertilization, to culture them, and to inject them into the patient's diseased or damaged organ. Since such cells carry different DNA from that of the patient, they could be used to treat genetic disorders. On the other hand, this means that precautions would have to be taken to avoid rejection.

Transplantation of immature nerve cells and stem cells from the brains of aborted human embryos has been used for several years to treat the degenerative brain condition, Parkinson's disease, with reasonably encouraging results. Such treatment has not greatly alleviated the characteristic tremor of the hands, and some patients have developed disturbing unintended movements. But most have regained the ability to initiate and control their actions. It is probable that embryonic stem cell injection will soon be used in efforts to treat the degenerative diseases Huntington's disease and Alzheimer's, and even stroke, in which parts of the brain are destroyed becomes of interruption of the blood supply.

There is wide agreement among medical scientists that research on human embryonic stem cells is an important first step towards stem cell therapy, even though it may eventually be possible to use adult stem cells. Yet the prospect of harvesting cells from living human embryos smacks of Frankenstein or Brave New World, and ‘pro-life’ religious groups have mounted stout moral opposition. However, it would not be necessary to fertilize additional human eggs specifically for such research. Present methods for the production of ‘test-tube babies’ involve the production and storage (by freezing) of several fertilized eggs, the unwanted ones simply being destroyed or permanently stored. These surplus eggs could, with parental agreement, provide a ready source of embryos for stem cell collection. Moreover, as long as there are strict limits on the time for which the embryo is allowed to develop, it will have no nervous system or other organs, no possibility of feelings, and nothing approaching an independent life. Also, the indubitable suffering of the many people who might be helped by stem cell therapy ought to weigh heavily in the complex moral equation.

In 2001, the British government authorized stem cell research on human embryos up to 14 days post-conceptual age. Given the huge potential benefits of stem cell therapy, it is likely that other nations will follow suit.

— Colin Blakemore

Bibliography

Further reading:

  • Thomson, J. et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145-1147.
  • US National Institutes of Health website. Stem cells: a primer. http: //www.nih.gov/news/stemcell/primer.htm

See also: antenatal development; assisted reproduction; cloning; disease; gene therapy; genetics, human; organ donation; pregnancy; transplantation.

 
Britannica Concise Encyclopedia: stem cell

In living organisms, an undifferentiated cell that can produce other cells that eventually make up specialized tissues and organs. There are two major types of stem cells, embryonic and adult. Embryonic stem cells are located in the inner mass of a blastocyst (an embryo at a very early stage of development), and they eventually give rise to every cell type of the adult organism. Adult stem cells are found in some tissues in the adult body, such as the epidermis of the skin, the lining of the small intestine, and the bone marrow, where they serve in the regeneration of old or worn tissue. In cancer treatment, blood-forming adult stem cells are routinely harvested from bone marrow, stored, and then reinfused into patients to replace blood cells destroyed by chemotherapy or radiation therapy. This potential for replacing damaged tissues has aroused great interest in using embryonic stem cells to treat a number of other conditions, such as Parkinson disease, severe burns, and damage to the spinal cord. Mouse embryonic stem cells are widely used to create genetically modified mice that serve as models for investigating human disease. However, the use of human embryonic stem cells, which requires destroying the blastocysts from which they are obtained, has raised objections by those who feel blastocyst-stage embryos are human beings. The first human stem cell line was created in 1998, using cells harvested from embryos produced through in vitro fertilization. The use of human embryonic stem cells is allowed in some countries and prohibited or restricted in others.

For more information on stem cell, visit Britannica.com.

 
Columbia Encyclopedia: stem cells,
unspecialized human or animal cells that can produce mature specialized body cells and at the same time replicate themselves. Embryonic stem cells are derived from a blastocyst (the blastula typical of placental mammals; see embryo), which is very young embryo that contains 200 to 250 cells and is shaped like a hollow sphere. The stem cells themselves are the cells in the blastocyst that ultimately would develop into a person or animal. “Adult” stem cells are derived from the umbilical cord and placenta or from blood, bone marrow, skin, and other tissues. The similar embryonic germ line cells come from a fetus that is 5 to 9 weeks old and are derived from tissue that would have developed into the ovaries or testes.

Medical researchers are interested in using stem cells to repair or replace damaged body tissues because stem cells are less likely than other foreign cells to be rejected by the immune system when they are implanted in the body. Embryonic stem cells have the capacity to develop into every type of tissue found in an adult; germ line cells and adult stem cells are less versatile. The processes that control such development, however, are not understood at present. Stem cells have been used experimentally to form the hematopoietic (blood-making) cells of the bone marrow; heart, blood vessel, muscle, and insulin-producing tissue; and sperm cells. Embryonic germ line cells have been used to help paralyzed mice regain some of the ability to move. Since the 1990s umbilical cord blood stem cells have sometimes been used to treat heart and other defects in children who have rare metabolic diseases and to treat children with certain anemias and leukemias. It has been shown that stem cells from this blood can migrate to damaged tissues and repair them.

Human stem cells have typically been extracted from surplus fertilized embryos produced during in vitro fertilization procedures. Some experimenters, however, have used embryos that were fertilized especially to produce stem cells. In so-called therapeutic cloning a nucleus from a patient's body cell, such as a skin cell, would be inserted into an egg that has had its nucleus removed to produce a blastocyst whose stem cells could be used to create tissue that would be compatible with that of the patient. Such a procedure was reported in 2005 to have been successfully undertaken in part by South Korean researchers who produced stem cell lines using genetic material from patients, but the data was subsequently shown to have been fabricated. (It was later determined, however, that the laboratory had produced stem cells using an egg that had developed through parthenogenesis, which does not involve fertilization or result in a viable human embryo.) Because extraction of embryonic stem cells destroys the embryo, the use of embryonic stem cells has been opposed by opponents of abortion.

The first embryonic stem cells to be isolated were extracted by British researchers from mouse blastocysts; the first human stem cells isolated and cultured were extracted by American scientists in 1998. In 1994 a National Institutes of Health (NIH) panel argued that creating human embryos for use in certain experiments might be justified, but Congress subsequently enacted (1995) a ban on federal financing for research involving human embryos in reaction to that report. The Dept. of Health and Human Services ruled in 1999, however, that that ban did not apply to financing work with stem cells, and guidelines for financing such research were issued by NIH the next year.

President George W. Bush, who had campaigned against financing embryonic stem cell research, announced in Aug., 2001, that he would support federal funding of research with embryonic stem cells, but only with the estimated 60 stem cell lines then existing. Some scientists challenged the assumption that these 60 stem cell lines would be sufficient for experimental and therapeutic needs, while others said the figure included some stem cell lines that had not yet been determined to be viable. In fact, in 2004, there were only 15 approved stem cell lines available to researchers funded by the U.S. government. The restrictions have not prevented other researchers, in the United States and elsewhere, from developing new embryonic stem cell lines and undertaking research with them using private funding, and California voted (2004) to create a $3 billion fund to underwrite embryonic stem cell research. A federal legislation that would have expanded the number of stem cell lines available for federally funded research was vetoed by the President Bush in July, 2006.

See also fetal tissue implant.

 
Science Dictionary: stem cell

A cell from which a variety of other cells can develop through the process of cellular differentiation. Stem cells can produce only a certain group of cells (as with skin stem cells) or any cell in the body (as with embryonic stem cells).

  • A major controversy involves the question of whether nonembryonic stem cells should be used for medical purposes.

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    Wikipedia: stem cell
    Mouse embryonic stem cells with fluorescent marker.
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    Mouse embryonic stem cells with fluorescent marker.
    Human Embryonic Stem cell colony on mouse embryonic fibroblast feeder layer.
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    Human Embryonic Stem cell colony on mouse embryonic fibroblast feeder layer.

    Stem cells are primal cells found in all multi-cellular organisms. They retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types. Research in the human stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960s.[1][2]

    The three broad categories of mammalian stem cells are: embryonic stem cells, derived from blastocysts, adult stem cells, which are found in adult tissues, and cord blood stem cells, which are found in the umbilical cord. In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells.

    As stem cells can be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed. In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates.[3]

    Stem cell properties

    Defining properties

    The rigorous definition of a stem cell requires that it possesses two properties:

    • Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
    • Unlimited potency - the capacity to differentiate into any mature cell type. In a strict sense, this requires stem cells to be either totipotent or pluripotent, although some multipotent and/or unipotent progenitor cells are sometimes referred to as stem cells.

    These properties can be illustrated in vitro, using methods such as clonogenic assays, where the progeny of a single cell is characterized.[4][5] However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.

    Potency definitions

    Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.
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    Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.

    Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.

    • Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.
    • Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.
    • Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).
    • Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells.

    Embryonic stem cells

    Main article: Embryonic stem cell

    Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos [6]. A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to 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 when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.

    Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF).[7] Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).[8] Without optimal culture conditions or genetic manipulation,[9] embryonic stem cells will rapidly differentiate.

    A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[10] The cell surface proteins most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[11]

    After twenty years of research, there are no approved treatments or human trials using embryonic stem cells. Their tendency to produce tumors and malignant carcinomas, cause transplant rejection, and form the wrong kinds of cells are just a few of the hurdles that embryonic stem cell researchers still face.[12] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.

    Adult stem cells

    Main article: Adult stem cell
    Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation
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    Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation

    The term adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults[13]. Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.[14] Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).[15][16]

    A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.[17] In mice, pluripotent stem cells can be directly generated from adult fibroblast cultures.[18]

    While embryonic stem cell potential remains untested, adult stem cell treatments have been used for many years to treat successfully leukemia and related bone/blood cancers through bone marrow transplants.[19] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Consequently, more US government funding is being provided for adult stem cell research[20].

    Lineage

    Main article: Stem cell line

    To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[21]

    An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals dpp and adherins junctions that prevent germarium stem cells from differentiating[22][23].

    The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.[24] However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.

    Treatments

    Main article: Stem cell treatments

    Medical researchers believe that stem cell therapy has the potential to change radically the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia.[25] In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries, and muscle damage, amongst a number of other impairments and conditions.[26][27] However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research.

    Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself. [28]

    Controversy surrounding stem cell research

    Main article: Stem cell controversy

    There exists a widespread controversy over stem cell research that emanates from the techniques used in the creation and usage of stem cells. Human embryonic stem cell research is particularly controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. However, recently, it has been shown in principle that embryonic stem cell lines can be generated using a single-cell biopsy similar to that used in preimplantation genetic diagnosis that may allow stem cell creation without embryonic destruction.[29]

    Opponents of the research argue that embryonic stem cell technologies are a slippery slope to reproductive cloning and can fundamentally devalue human life. Those in the pro-life movement argue that a human embryo is a human life and is therefore entitled to protection.

    Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for in vitro fertilisation could be donated with consent and used for the research.

    The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge.

    Key stem cell research events


    Stem cell funding & policy debate in the US

    • 1995 - U.S. President Bill Clinton signs into law the Dickey Amendment which prohibited federally appropriated funds to be used for research where human embryos would be either created or destroyed.
    • 02 November, 2004 - California voters approve Proposition 71, which provides $3 billion in state funds over ten years to human embryonic stem cell research.
    • 2001-2006 - U.S. President George W. Bush endorses the Congress in providing federal funding for embryonic stem cell research of approximately $100 million as well as $250 million for research on adult and animal stem cells. He also enacts laws that restrict federally-funded stem cell research on embryonic stem cells to the already derived cell lines.
    • 5 May, 2006 - Senator Rick Santorum introduces bill number S. 2754, or the Alternative Pluripotent Stem Cell Therapies Enhancement Act, into the U.S. Senate.
    • 18 July, 2006 - The U.S. Senate passes the Stem Cell Research Enhancement Act H.R. 810 and votes down Senator Santorum's S. 2754.
    • 19 July, 2006 - President George W. Bush vetoes H.R. 810 (Stem Cell Research Enhancement Act), a bill that would have reversed the Clinton-era law which made it illegal for federal money to be used for research where stem cells are derived from the destruction of an embryo.
    • 07 November, 2006 - The people of the U.S. state of Missouri passed Amendment 2, which allows usage of any stem cell research and therapy allowed under federal law, but prohibits human reproductive cloning.[37]
    • 16 February, 2007 – The California Institute for Regenerative Medicine became the biggest financial backer of human embryonic stem cell research in the United States when they awarded nearly $45 million in research grants. [38]

    See also

    References

    1. ^ Becker AJ, McCulloch EA, Till JE (1963). "Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells". Nature 197: 452-4. DOI:10.1038/197452a0. PMID 13970094. 
    2. ^ Siminovitch L, McCulloch EA, Till JE (1963). "The distribution of colony-forming cells among spleen colonies". Journal of Cellular and Comparative Physiology 62: 327-36. PMID 14086156. 
    3. ^ Tuch BE (2006). "Stem cells--a clinical update". Australian family physician 35 (9): 719-21. PMID 16969445. 
    4. ^ Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow IA (1974). "Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method". Exp Hematol 2 (2): 83-92. PMID 4455512. 
    5. ^ Friedenstein AJ, Gorskaja JF, Kulagina NN (1976). "Fibroblast precursors in normal and irradiated mouse hematopoietic organs". Exp Hematol 4 (5): 267-74. PMID 976387. 
    6. ^ http://www.foxnews.com/story/0,2933,210078,00.html
    7. ^ [1] , Mouse Embryonic Stem (ES) Cell Culture-Current Protocols in Molecular Biology
    8. ^ [2], Culture of Human Embryonic Stem Cells (hESC) NIH
    9. ^ Chambers I, Colby D, Robertson M, et al (2003). "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells". Cell 113 (5): 643-55. DOI:10.1016/S0092-8674(03)00392-1. PMID 12787505. 
    10. ^ Boyer LA, Lee TI, Cole MF, et al (2005). "Core transcriptional regulatory circuitry in human embryonic stem cells". Cell 122 (6): 947-56. DOI:10.1016/j.cell.2005.08.020. PMID 16153702. 
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