Freinds,

I tried to forward a Science Week article on the state of embryonic
stem cell research, but I ran afoul of the list's 500 line limit.
The article is of possible interest to this list due to the tie-in to
embryonic nerve cell transplants.  With a line of stem cells of the
proper type, one could conceivably have an unlimited amount of
transplant material.  All still very researchy, of course.

To get around the limit of the list I'm going to try forwarding it in
two segments.  I can't edit it down, since the redistribution
permission forbids changes.

Bill

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From: "Science-Week" <[log in to unmask]>
Organization: Science-Week
To: [log in to unmask]
Date: Fri, 24 Dec 1999 08:11:43 -0600
Subject: Science Week BULLETIN December 20, 1999

ScienceWeek BULLETIN - December 20, 1999
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Science & Society: Ammonia and the Population Explosion
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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 [[log in to unmask]]
-----------
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 [[log in to unmask]]
-----------
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
-------------------

[continued in part 2...]