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Stem cell

2007 Schools Wikipedia Selection. Related subjects: General Biology; Health
and medicine

   Mouse embryonic stem cells with fluorescent marker.
   Enlarge
   Mouse embryonic stem cells with fluorescent marker.

   Stem cells are primal cells that retain the ability to renew themselves
   through cell division and can differentiate into a wide range of
   specialized cell types. Research in the stem cell field grew out of
   findings by Canadian scientists Ernest A. McCulloch and James E. Till
   in the 1960s. The two categories of stem cells are embryonic stem
   cells, derived from blastocysts and adult stem cells, derived from
   umbilical cord blood or bone marrow. In a blastocyst of a developing
   embryo, stem cells differentiate into all of the specialised 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 readily grown and transformed into specialized tissues
   such as muscles or nerves through cell culture, their use in medical
   therapies has been proposed.

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 makes stem cells 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 single cell is characterized.
   However, in vitro culture conditions can alter the behaviour 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

   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 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

   Embryonic stem cells (ES cells) are stem cells derived from the inner
   cell mass of a blastocyst. A blastocyst is an early stage embryo -
   approximately 4 to 5 days old in humans and consisting of 50-150 cells.
   ES cells are pluripotent, and give rise during development of 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.

   When given no stimuli for differentiation, ES cells will continue to
   divide in vitro and each daughter cell will remain pluripotent. The
   pluripotency of ES cells has been rigorously demonstrated in vitro and
   in vivo, thus they can be indeed classified as stem cells.

   Bold text''''Because of their unique combined abilities of unlimited
   expansion and pluripotency, embryonic stem cells are a potential source
   for regenerative medicine and tissue replacement after injury or
   disease. To date, no approved medical treatments have been derived from
   embryonic stem cell research. This is not surprising considering that
   many nations currently have a moratorium on either ES cell research or
   the production of new ES cell lines.'

Adult stem cells

   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
   Enlarge
   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

   Adult stem cells are undifferentiated cells found throughout the body
   that divide to replenish dying cells and regenerate damaged tissues.
   Also known as somatic (from Greek Σωματικóς, of the body) stem cells,
   they can be found in children, as well as adults.

   A great deal of adult stem cell research has focused on clarifying
   their capacity to divide or self-renew indefinitely and their
   differentiation potential. Many adult stem cells may be better
   classified as progenitor cells, due to their limited capacity for
   cellular differentiation.

   Nevertheless, specific multipotent or even unipotent adult progenitors
   may have potential utility in regenerative medicine. 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. In contrast with the embryonic stem cell
   research, more US government funding has been provided for adult stem
   cell research. Adult stem cells can be isolated from a tissue sample
   obtained from an adult. They have mainly been studied in humans and
   model organisms such as mice and rats.

Lineage

   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. Progentiors can go through several rounds of cell division
   before terminally differentiating into a mature cell. It is believed
   that the molecular distinction between symmetric and asymmetric
   divisions lies in differential segregation of cell membrane proteins
   (such as receptors) between the daughter cells.

Treatments

   Medical researchers believe that stem cell research has the potential
   to change the face of human disease. A number of current treatments
   already exist, although the majority of them are not commonly used
   because they tend to be experimental and not very cost-effective.
   Medical researchers anticipate being able to use technologies derived
   from stem cell research to treat cancer, parkinson's disease, spinal
   cord injuries, and muscle damage, amongst a number of other diseases,
   impairments and conditions. 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.

Controversy surrounding stem cell research

   There exists a widespread controversy over stem cell research that
   emanates from the techniques used in the creation and usage of stem
   cells. 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. Opponents of the research argue that this practice is a
   slippery slope to reproductive cloning and tantamount to the
   instrumentalization of a human being. Contrarily, medical researchers
   in the field argue that it is necessary to pursue embryonic stem cell
   research because the resultant technologies are expected to have
   significant medical potential, and that the embryos used for research
   are only those slated for destruction anyway. 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 events in stem cell research

     * 1960s - Joseph Altman and Gopal Das present evidence of adult
       neurogenesis, ongoing stem cell activity in the brain; their
       reports contradict Cajal's "no new neurons" dogma and are largely
       ignored
     * 1963 - McCulloch and Till illustrate the presence of self-renewing
       cells in mouse bone marrow
     * 1968 - bone marrow transplant between two siblings successfully
       treats SCID
     * 1978 - haematopoietic stem cells are discovered in human cord blood
     * 1981 - mouse embryonic stem cells are derived from the inner cell
       mass
     * 1992 - neural stem cells are cultured in vitro as neurospheres
     * 1995 - 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.
     * 1997 - leukemia is shown to originate from a haematopoietic stem
       cell, the first direct evidence for cancer stem cells
     * 1998 - James Thomson and coworkers derive the first human embryonic
       stem cell line at the University of Wisconsin-Madison.
     * 2000s - several reports of adult stem cell plasticity are published
     * 2003 - Dr. Songtao Shi of NIH discovers new source of adult stem
       cells in children's primary teeth
     * 2004-2005 - Hwang Woo-Suk claims to have created several human
       embryonic stem cell lines from unfertilised human oocytes. The
       lines are later shown to be fabricated
     * 2005 - Researchers at Kingston University in England claim to have
       discovered a third category of stem cell, dubbed cord-blood-derived
       embryoniclike stem cells (CBEs), derived from umbilical cord blood.
       The group claims these cells are able to differentiate into more
       types of tissue than adult stem cells.
     * 2001-2006 - President George W. Bush endorses the United States
       Congress in providing limited federal funding for embryonic stem
       cell research totalling approximately $100 million. At the same
       time, he also enacts laws that restrict federally funded stem cell
       research on embryonic stem cells to the already derived but
       dwindling cell lines. Bush also endorsed funding for a total of
       $250 million dollars for research on adult and animal stem cells.
     * July 19, 2006 - President George W. Bush vetoes H.R. 810, 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.

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