[...continued from part 1]

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 [[log in to unmask]]
-----------
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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