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> ScienceWeek BULLETIN - December 20, 1999
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> SW BULLETIN - December 20, 1999
> ---------------------------------------------
> 
> This Week's Report:
> 
> Science Policy: Human Embryonic Stem Cell Research
> 
> ---------------------------------------------
> 
> [The following report first appeared in ScienceWeek 20 Aug 99]
> 
> ON HUMAN EMBRYONIC STEM CELL RESEARCH
> In a multicellular living organism such as a human or a mouse,
> what differentiates one cell type from another is apparently not
> the genome, since the genome is the same in every cell, but which
> parts of the genome are operational. In other words, each cell
> type, skin cell, muscle cell, etc., has a particular gene profile
> characteristic of that cell type. Cells of a particular cell type
> are said to be "differentiated". Stem cells, present in all early
> embryos and in some tissues, are undifferentiated cells that in
> response to appropriate signals differentiate and give rise to a
> variety of cell types. Embryonic stem cells are "totipotent",
> i.e., they have the potential to differentiate into any type of
> tissue cell. These cells form at a very early stage in human
> development and remain in an undifferentiated state for only a
> short period of time. They are first clearly recognizable
> approximately 5 to 7 days after fertilization, when a human
> embryo forms a structure called a "blastocyst", a hollow fluid-
> filled sphere consisting of only 140 cells. There are two types
> of cells in the blastocyst at this stage: a) "trophoblast cells",
> which form the wall of the sphere, and which will become
> supporting tissues of the fetus (e.g., the placenta); b) "inner-
> cell-mass cells", a clump of cells located at one end within the
> blastocyst interior, and which are the undifferentiated cells
> (stem cells) that will divide and develop into the individual.
> The expected future medical applications of stem cells,
> particularly embryonic stem cells, are extremely promising, but
> because of the involvement of embryos and certain other
> considerations, basic stem cell research has provoked intense
> controversy. ... ... Shirley J. Wright (University of Dayton, US)
> presents a review of those aspects of human embryonic stem cell
> research that have been the focus of science policy controversy,
> the author making the following points:
>      1) Human blastocysts -- each capable of developing into a
> complete human being -- are a potential source of embryonic stem
> cells, undifferentiated cells with the potential to develop into
> any cell type in the body. These cells have enormous therapeutic
> potential for the replacement of damaged or diseased tissues, but
> current legal and ethical concerns limit the nature of the
> research that can be performed with these cells because of their
> source.
>      2) At the 5 day stage, the human blastocyst is approximately
> 200 microns in diameter. Cells of the inner cell mass can give
> rise to all 3 germ layers -- the ectoderm, mesoderm, and endoderm
> -- which in turn give rise to all the tissues in the body. The
> ectoderm cells develop into skin, nerves and eyes; the mesoderm
> cells develop into bone, blood, and muscles; the endoderm cells
> develop into the lungs, liver, and the lining of the intestines.
> At the 5 to 7 day stage, the inner cell mass can be removed from
> the blastocyst and cultured in a dish as embryonic stem cells.
>      3) Early human embryos can also provide undifferentiated
> pluripotent cells (i.e., cells capable of differentiating into
> certain cell types but not all cell types) in the form of
> primordial germ cells, the precursors of eggs and sperm cells.
> The primordial germ cells do not differentiate early, remaining
> in the yolk sac until approximately the 6th to 8th week of
> development, when they migrate to the developing gonads in the
> embryo. These primordial germ cells may be extracted as
> pluripotent embryonic germ cells beginning approximately 24 days
> after fertilization.
>      4) Embryonic stem cells obtained from the inner cell mass of
> a blastocyst can be grown in a culture dish on a layer of
> "feeder" cells derived from irradiated mouse *fibroblasts. The
> layer of feeder cells arrests the differentiation of the stem
> cells by releasing various inhibitory factors. Cell lines derived
> in this manner are immortal -- they can divide indefinitely to
> form more undifferentiated cells, thus providing a ready source
> for future research.
>      5) Fusing a human somatic cell (i.e., any human non-germ
> cell) with an enucleated egg cell allows the creation of person-
> specific embryonic stem cells, thus avoiding the complications of
> tissue incompatibility. In this technique, a patient's somatic
> cell is placed next to an enucleated egg cell, and the two cells
> are fused by application of an electric current, the somatic cell
> nucleus entering the egg cytoplasm. The egg is then activated and
> develops into a blastocyst embryo, and the blastocyst can now
> provide embryonic stem cells compatible with the patient. This is
> the technique that was used Ian Wilmut and his group to produce
> the cloned sheep Dolly.
>      6) Transfer of a human somatic-cell nucleus (such as a cheek
> *epithelial-cell nucleus) to an enucleated bovine egg cell
> produces a "*chimera" that could be the source of embryonic stem
> cells. Such an experiment was successfully performed by Robl and
> Cibelli in 1996. The embryo developed to the 32-cell stage, but
> was not allowed to develop further.
>      7) Production of human replacement tissue (e.g., neural
> cells, pancreatic cells, or heart-muscle cells) in a culture dish
> is one of the important potential clinical applications of
> embryonic stem-cell technology. Once cultured, the differentiated
> cells would be injected into the damaged organ, where they would
> replace the damaged tissue. But this has not yet been achieved,
> and the clinical technology will require years of development.
>      8) The author concludes: "As a society we must identify the
> ethical, social, legal, medical, theological, and moral issues
> that surround this research. People from all walks of life --
> scientists, lawyers, ethicists, clergy, and the general public --
> should be involved in making the decision. We are also at the
> crossroads where further scientific evidence is needed to explore
> the full potential of these cells, and yet many of the necessary
> experiments raise further ethical issues. The question of how we
> should use these powerful cells remains a challenging problem for
> the next century."
> -----------
> Shirley J. Wright: Human embryonic stem-cell research: Science
> and ethics.
> (Amer. Scientist Jul/Aug 99 87:352)
> QY: Shirley J. Wright [[EMAIL PROTECTED]]
> -----------
> Text Notes:
> ... ... *fibroblasts: A type of connective tissue cell, secreting
> structural proteins (e.g., collagen) that form certain tissue
> components, including the extracellular matrix.
> ... ... *epithelial-cell: In animals, epithelial cells
> (epithelium) compose the cell layers that form the interface
> between a tissue and the external environment, for example, the
> cells of the skin, the lining of the intestinal tract, and the
> lung airway passages.
> ... ... *chimera: In general, a "chimera" is any cell or organism
> with genetic material from two or more genotypes (e.g., two or
> more species). 
> -------------------
> Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 20Aug99
> -------------------
> Related Background:
> PATENT ON UMBILICAL-CORD STEM CELLS REJECTED IN EUROPE
> Stem cells are undifferentiated cells that give rise to all the
> varieties of cells. Bone marrow stem cells are undifferentiated
> cells in bone marrow that give rise to all the varieties of blood
> cells, including the various leukocytes (white blood cells) of
> the immune system: B-cells, T-cells, and macrophages. Umbilical
> cord stem cells can produce red and white blood cells and
> platelets, and their transplantation is more effective and
> cheaper than conventional methods involving stem cells from bone
> marrow donors. Umbilical cord stem cells, for example, have lower
> immunogenicity, which reduces the risk of rejection by the
> patient. A group of international researchers and international
> biotechnology companies have won a legal challenge against a
> European patent on the use of stored umbilical cord stem cells.
> The patent was granted 3 years ago to the US company Biocyte, but
> it has now been rejected in Europe, with the primary reason for
> the rejection apparently the existence of previous use of such
> cells by others. Researchers in the field say the winning of this
> legal battle lifts the threat of expensive patent infringement
> litigation, a threat that has intimidated the exploration of new
> uses for umbilical cord blood cells.
> (Nature 99/399:626) (SW Bulletin 25 Jun 99)
> -------------------
> Related Background:
> CONVERSION OF NEURAL STEM CELLS INTO BLOOD CELLS
> ... Stem cells are common in embryos, but they have also been
> identified in adult tissues that undergo extensive cell
> replacement due to physiological turnover or injury, e.g., the
> *hematopoietic, intestinal, and *epidermal systems. Stem cells
> have also been found in the central nervous system, a tissue
> believed to be capable of only extremely limited self-repair.
> Central nervous system stem cells can generate the 3 major cell
> types found in the adult brain: *astrocytes, *oligodendrocytes,
> and neurons. This is consistent with the view that the
> developmental potential of stem cells is restricted to the
> differentiated elements of the tissue in which they reside. But
> some developmental peculiarities suggest certain cells may be
> able to differentiate into cell types that are not of the same
> origin. ... ... C.R.R. Bjornson et al (5 authors at 4
> installations, CA IT) now report an investigation to determine
> whether stem cells are restricted to produce specific cell types,
> namely, those from the tissue in which they reside. The authors
> report that after transplantation into *irradiated host mice,
> genetically labelled mouse neural stem cells were found to
> produce a variety of blood cell types, including *myeloid and
> *lymphoid cells, as well as early hematopoietic cells. The
> authors suggest that neural stem cells appear to have a wider
> differentiation potential than previously thought, and that if
> they behave similarly to their mouse counterparts, human neuronal
> stem cells may provide a renewable and characterized source of
> cells that could be used in approaches aimed at hematopoietic
> reconstitution in various blood diseases and disorders.
> -----------
> C.R.R. Bjornson et al: Turning brain into blood: A hematopoietic
> fate adopted by adult neural stem cells in vivo.
> (Science 22 Jan 99 283:534)
> QY: Christopher R.R. Bjornson [[EMAIL PROTECTED]]
> -----------
> Text Notes:
> ... ... *hematopoietic: From hematopoiesis (hemopoiesis,
> hematogenesis) Refers to the formation and development of the
> various types of blood cells. 
> ... ... *epidermal: The term "epidermal" refers to the
> superficial epithelial portion of the skin. In animals,
> epithelial cells compose the cell layers that form
> the interface between a tissue and the external environment, for
> example, the cells of the skin, the lining of the intestinal
> tract, and the lung airway passages.
> ... ... *astrocytes: (astroglia, macroglia) Glial cells are more
> numerous than neurons in the brain, but their function has been
> generally characterized as "metabolic" or "supportive", without
> much discussion of details. Astrocytes are the largest glial
> cells, with many extensions radiating outward like a starburst,
> and at least one of their functions is apparently to maintain the
> so-called "blood-brain barrier" effectively separating neural
> tissue from blood.
> ... ... *oligodendrocytes: (oligodendroglia) Glial cells
> characterized by sheet-like processes that are wrapped around
> individual neuron axons to form the myelin sheath of nerve fibers
> in the central nervous system. (The myelin sheath of a nerve
> fiber is effectively a periodically interrupted insulation which
> increases the propagation velocity of nerve impulses.)
> ... ... *irradiated host mice: In this investigation, host
> animals were radiated before transplantation in order to reduce
> the population of immune system blood cells, this reduction
> apparently intensifying the signals resulting in donor stem cell
> differentiation.
> ... ... *myeloid: Refers to bone marrow cells or cells derived
> from bone marrow cells.
> ... ... *lymphoid cells: Refers to cells of the lymphatic system.
> The lymphatic system is a complex network for the distribution of
> lymph fluid (which is similar to blood plasma -- blood without
> red cells).
> -------------------
> Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Apr99
> -------------------
> Related Background:
> RESEARCH USE OF STEM CELLS APPROVED BY NIH
> It is probable that one of the major public debates in the coming
> months will concern the use of human stem cells in research (see
> related background report below). On 19 January 1999, the US
> Department of Health and Human Services announced that a
> Congressional ban on human embryo research does not apply to
> human stem cells, and federally financed researchers will soon
> be able to work on these cells. In its ruling, the Office of
> the General Counsel of the US health department said that because
> stem cells by themselves do not have the capacity to develop into
> a human being, they cannot be considered embryos. Deriving the
> cells from human embryos is legal, provided it is not done with
> federal money. Harold E. Varmus, director of the US National
> Institutes of Health, has stated it would still be illegal for
> researchers to use federal money to derive their own stem cells
> from human embryos, but they can now use federal money to work on
> the cells obtained by others, in particular the stem cells
> obtained by James Thompson (University of Wisconsin, US) from
> human embryos created in surplus amounts in a fertility clinic.
> The new US government ruling on the use of human stem cells is
> opposed by the US National Conference of Catholic Bishops, and
> the ruling is still subject to modification or elimination by the
> new US Congress.
> (New York Times 20 Jan 1999)
> -------------------
> Summary by SCIENCE-WEEK [http://scienceweek.com] 29Jan99
> -------------------
> Related Background:
> EMBRYONIC STEM CELLS DERIVED FROM HUMAN BLASTOCYSTS
> *Embryonic stem cells are derived from *totipotent cells of the
> early mammalian embryo and are capable of *unlimited and
> undifferentiated proliferation in vitro. In *chimeras with intact
> embryos, mouse embryonic stem cells contribute to a wide range of
> adult tissues, including *germ cells, providing a powerful
> approach for introducing specific genetic changes into the mouse
> *germ line. ... ... J.A. Thompson et al now report the production
> of human *blastocyst-derived *pluripotent cell lines that have
> normal chromosome characteristics, express high levels of
> *telomerase activity, and express *cell surface markers that
> uniquely characterize primate embryonic stem cells. The authors
> report that after undifferentiated proliferation in vitro for 4
> to 5 months, these cells still maintained the developmental
> potential to form *trophoblast, and to form derivatives of *all 3
> embryonic germ layers, including gut *epithelium (mesoderm) and
> neural epithelium, embryonic *ganglia, and *stratified squamous
> epithelium (ectoderm). The authors suggest these cell lines
> should be useful in human developmental biology, drug discovery,
> and transplantation medicine. ... ... In a related commentary in
> the same journal, J. Gearhart makes the following points: 1) A
> renewable tissue-culture source of human cells capable of
> differentiating into a wide variety of cell types would have
> broad applications in basic research and transplantation
> therapies. A major step in realizing this goal has now been taken
> with the demonstration that human embryonic stem cells can be
> grown in culture. 2) In the work of J.A. Thompson et al, four
> cell lines tested produced *teratomas when grown in
> *immunosuppressed mice. Histology of the tumors revealed
> differentiated cells derived from all 3 embryonic germ layers
> (ectoderm, mesoderm, and definitive endoderm) -- a result
> consistent with pluripotency. 3) The derivation of human
> embryonic stem cells now raises a whole new set of expectations.
> On the basis of the already completed use and study of mouse
> embryonic stem cells, the research and clinical potential for
> human embryonic stem cells is enormous. They will be important
> for in vitro studies of normal human embryogenesis, abnormal
> development (through the generation of cell lines with targeted
> gene alterations and engineered chromosomes), human gene
> discovery, drug and *teratogen testing, and as a renewable source
> of cells for tissue transplantation, cell replacement, and gene
> therapies. These latter applications could eventually make
> unnecessary the direct use of fetal tissue in transplantation
> therapies [*Note #1].
> -----------
> J.A. Thompson et al (7 authors at 2 installations, US IL)
> Embryonic stem cell lines derived from human blastocysts.
> (Science 6 Nov 98 282:1145)
> QY: James A. Thompson, University of Wisconsin 608-262-3961.
> -----------
> J. Gearhart (Johns Hopkins University, US)
> New potential for human embryonic stem cells.
> (Science 6 Nov 98 282:1061)
> QY: John Gearhart [[EMAIL PROTECTED]]
> -----------
> Text Notes:
> ... ... *Embryonic stem cells: In general, the term "stem cells"
> refers to undifferentiated cells that upon differentiation can
> give rise to various specialized cell lines such as blood cells,
> skin cells, nerve cells, etc. Adult bone marrow, for example,
> contains stem cells that are the precursors of the various
> specialized types of blood cells. "Embryonic" stem cells are
> specifically stem cells derived from the embryo only.
> ... ... *totipotent cells: Cells that have the ability to
> differentiate into any type of cell and thus form a new organism
> or regenerate any part of an organism.
> ... ... *unlimited and undifferentiated proliferation in vitro:
> In general, differentiated "normal" cells in tissue culture
> produce a limited number of replications. In contrast, embryonic
> stem cells and many types of cancer cells in tissue culture show
> unlimited replications, and are thus called "immortal" cell
> lines. In this context, "undifferentiated" proliferation is
> simply proliferation without cell differentiation
> (specialization).
> ... ... *chimeras: In this context, an animal that has received a
> transplant of genetically and immunologically different tissue.
> In this report, the transplant involves the injection of human
> cultured stem cells into mice.
> ... ... *germ cells: In general, reproductive cells. All other
> cells are "somatic" cells.
> ... ... *germ line: In general, this refers to the line of
> differentiated germ cells.
> ... ... *blastocyst: A mammalian egg in the later stages of
> *cleavage but before implantation in the uterus. The blastocyst
> consists of a hollow fluid-filled ball of cells and an inner cell
> mass (embryonic stem cells) from which the embryo develops.
> ... ... *cleavage: The early and rapid division stage that
> divides the fertilized egg into smaller and smaller cells
> (blastomeres) while retaining the same overall size of the
> embryo.
> ... ... *pluripotent cell: A cell that has the potential,
> depending on conditions, to give rise to many differentiated cell
> lines but which lacks complete totipotency.
> ... ... *telomerase: Telomeres are defined ends of chromosomes
> that contain specific repeated DNA sequences. They are essential
> for normal chromosome replication, and since their length
> shortens a bit with each replication, they are believed to be
> involved in the aging of the cell. Telomerase is an enzyme that
> repairs damage to telomeres, and it is thought by some that
> cancerous cells may have mutant telomerase, the mutant enzyme
> conferring immortality on the cancer cell.
> ... ... *cell surface markers: Cell surface proteins or protein
> components that can be chemically identified.
> ... ... *trophoblast: In the early vertebrate embryo, the outer
> ectodermal cell layer of the blastocyst. In mammals, it is the
> trophoblast that attaches to the uterus and forms the placenta.
> ... ... *all 3 embryonic germ layers: In the embryos of higher
> animals, there occurs the transformation of a single-layer
> blastula into a 3-layered gastrula consisting of ectoderm,
> mesoderm, and endoderm surrounding a cavity with one opening. The
> 3 layers are called the "germ layer", and these layers, via
> further cell differentiation and proliferation, determine the
> development of all the major body systems and organs.
> ... ... *epithelium: In animals, epithelial cells (epithelium)
> compose the cell layers that form the interface between a tissue
> and the external environment, for example, the cells of the skin,
> the lining of the intestinal tract, and the lung airway passages.
> ... ... *ganglia: (singular: ganglion) In the context of cells,
> the original meaning of "ganglion" was any cluster of nerve cell
> bodies in the central or peripheral nervous system. Currently,
> the term "ganglion" refers to a aggregation of nerve cell bodies
> located in the peripheral nervous system. Unfortunately, many
> neuroanatomy texts still label certain neuron clusters in the
> central nervous system in the old way (e.g., basal ganglia).
> ... ... *stratified squamous epithelium:  The cells of the
> epithelium are for the most part closely packed cells with little
> extracellular material between adjacent cells, the cells arranged
> in continuous sheets in either single or multiple layers. The
> cells may be flat, cubelike, columnar, or a combination of
> shapes, and "squamous" cells are flattened and scalelike. In this
> context, "stratified squamous epithelium" refers to a structure
> consisting of distinctly layered epithelial cells (layers varying
> in size and shape of cells), the top layer of which are squamous
> cells.
> ... ... *teratomas: A teratoma is a neoplasm (tumor) composed of
> multiple tissues, including tissues not normally found in the
> organ in which it arises. A teratoma in the adult human ovary,
> for example, can contain hair, teeth, skin, heart muscle, nerve
> cells, and so on -- all a result of "wild" cellular
> differentiation of neoplastic cells, but with enough regulation
> so that distinct tissues are formed. In the context of this
> report, the teratomas occurred in mice after injection of
> cultured human stem cells, thus demonstrating the ability of
> those stem cells to differentiate into organized specific tissue-
> producing cells.
> ... ... *immunosuppressed mice: In general, this refers to mice
> whose immune system response has been suppressed by chemical,
> biological, or physical means. In this report, the purpose of the
> immunosuppression was to allow the development of a mouse
> teratoma provoked by injection of human stem cells. Without
> immunosuppression, the human stem cells would be immediately
> attacked and possibly destroyed by the mouse immune system before
> the stems cells could differentiate.
> ... ... *teratogen: Any drug or other agent that causes abnormal
> fetal development.
> ... ... *Note #1: We repeat here a quotation that appeared at the
> head of a recent issue of SW: "Between the fifth and tenth days
> the lump of stem cells differentiates into the overall building
> plan of the mouse embryo and its organs. It is a bit like a lump
> of iron turning into the space shuttle. In fact it is the
> profoundest wonder we can still imagine and accept, and at the
> same time so usual that we have to force ourselves to wonder
> about the wondrousness of this wonder." -- Miroslav Holub
> -------------------
> Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 27Nov98
> 
> [SW Bulletin 20 Dec 99]
> 
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> Contents of the current issue of ScienceWeek (24 December 99):
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> 1. Science Policy: On the Regulation of Human Genetic Tests
> 2. Applied Mathematics: Conformal Mapping
> 3. Astrophysics: On the Complexity of the Death of Stars
> 4. Neurobiology: Modification of Dendritic Spines by Calcium
> 5. Paleoanthropology: Dating of Late Pleistocene Hominid Remains
> 6. Evolutionary Biology: Two Species of Living Coelacanths
> In Focus: On the Foundations of Quantum Mechanics
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