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What is cell engineering?
Cell engineering encompasses a wide range of research and practical techniques
in science. Technically, any manipulation that disturbs a cell from its original,
natural state is cell engineering. For the Institute for Cell Engineering at
Johns Hopkins, the term refers not just to changing a cell in some perceivable
way, but to understanding how cells control their own destinies and then taking
advantage of or overcoming those natural processes in order to achieve a particular
change.
For example, one program at the Institute seeks to understand the biological
signals that direct stem cells to form a particular cell type out of the plethora
of possibilities -- a blood cell instead of a brain cell, for instance. The
researchers would then try to use the new information to produce a desired
cell type -- say a dopamine-producing brain cell for Parkinson's disease, or
an insulin-producing pancreatic cell for diabetes. It is important to note
that research with stem cells is only one subset of cell engineering.
Why pursue cell engineering?
Based on new information gained by scientifically rigorous testing, medicine
is constantly evolving and improving. Developments in genetics in the last
quarter of the 20th century revolutionized the way medicine is practiced compared
to the 1950s. Likewise, the scientists in the Institute for Cell Engineering
at Hopkins believe that cell engineering will generate a dramatic and fundamental
change in medicine over the next 25 years.
Just as basic research was (and still is) required to understand genes and
their involvement in disease, scientists need to understand the life path of
cells, how they might be convinced to switch paths, and how engineered cells
could be appropriately used to fix problems that lead to conditions like juvenile
diabetes (patients lack insulin-producing cells) or Parkinson's disease (patients'
dopamine-producing brain cells gradually die).
Importantly, diseases most applicable to stem cell therapies are those for
which few if any treatments exist currently and there are no chances for cures.
Thus, while basic knowledge gained from studying stem cell biology and other
biological aspects of cell differentiation is itself important, the work is
being watched closely because of its huge potential for changing -- and saving
-- the lives of many.
Multipotent, Pluripotent, Embryonic Stem Cells -- Help! I'm confused!
There are a lot of words used in stem cell research to distinguish between
different types of stem cells, different sources of stem cells, and the different
abilities of these various kinds of stem cells.
Stem cells themselves are cells found naturally in the body that provide a
back-up source for the body's various cell types. They're "primitive" or "precursor" cells
because they can renew themselves, but also possess the unusual ability to
become other, more specialized cell types. Different types of stem cells have
different natural limits on what they can become -- blood stem cells naturally
form only the different types of blood cells (red blood cells, white blood
cells and platelets), neuronal stem cells can become types of nerve and brain
cells (glial cells, astrocytes and neurons).
"Adult"stem cells don't necessarily come from fully-grown people.
Instead, the term refers to the status of the organ from which they are taken;
these types of stem cells come from established organs in fetal tissue, children
or adults. Taken from the placenta or from a person, blood stem cells (or hematopoietic
stem cells) have been used routinely for more than a decade to repopulate an
individual's blood supply after or as part of cancer treatment. New applications
of blood stem cells are being investigated at centers around the world for
conditions such as inherited metabolic disorders, autoimmune diseases and sickle
cell disease. Other types of "adult" stem cells have been discovered
more recently; even organs thought incapable of regenerating, such as the brain,
turn out to have their own specialized stem cells. Some evidence suggests that "adult" stem
cells may be more flexible in what they can become than previously thought,
but these early results still need to be verified.
Pluripotent stem cells are cells derived from embryos or fetuses and are naturally
capable of turning into any type of cell found in the body. There are two kinds
of pluripotent stem cells: embryonic stem cells, derived from embryos; and
embryonic germ cells, derived from fetuses. Despite the cells' different sources, "embryonic
stem cell" is often used to refer to both types of pluripotent stem cells
in non-scientific settings in the U.S.
Embryonic stem cells (ES cells) can become any of the body's various cell
types and are derived from the inner cell mass of pre-implantation embryos
originally created for in vitro fertilization (IVF) purposes. The inner cell
mass does not contained specialized cells when it is removed to obtain embryonic
stem cells, therefore each of its cells has the potential to form any of the
body's various tissues, providing dramatic possibilities for medicine. Even
if implanted into a uterus, a stem cell cannot become a child -- the cell lacks
information needed to organize and instead would form a certain kind of tumor
known as a teratoma. In the U.S., human embryonic stem cells were first isolated
and cultured in the laboratory of James Thomson at the University of Wisconsin.
Embryonic germ cells(EG cells) have the same characteristics as embryonic
stem cells -- they, too, can become any of the body's cell types -- but they
are derived from fetal tissue instead of IVF embryos. "Germ" refers
to the specific source of the cells: the developing gonadal ridge in 5- to
9-week-old aborted fetuses, a region that would eventually become the reproductive
organs. Like embryonic stem cells, embryonic germ cells also cannot create
a fetus if implanted into a uterus. In the U.S., human embryonic germ cells
were first isolated and cultured in the laboratory of John D. Gearhart at The
Johns Hopkins University School of Medicine, who is leader of ICE's program
in stem cell biology.
"Multipotent stem cells" usually refers to adult stem cells, since
they can become more than one type of cell but can't become all types of cells.
In particular, "multipotent" is used to describe adult stem cell
types that researchers have coaxed into unexpected cell types, although these
early observations must be verified. Multipotent stem cells might be useful
therapeutically for diseases in which the cells of only one organ need to be
replaced, such as diabetes (pancreatic islet cells) or neurological diseases
(such as dopamine-producing neurons in Parkinson's disease or motor neurons
in Lou Gehrig's disease).
Is one type of stem cell better than the others?
So little is understood about each of the types and sources of stem cells
that it is crucial for scientists to have access to all of them. Future studies
may reveal that different types of stem cells work better in different applications.
There's so much left to learn, it's practically impossible to predict what
might be discovered about cell and organism development as this basic research
continues.
Fundamentally, science succeeds when many researchers approach a common question
from a number of directions. For example, even with stem cells' possibilities
of future treatments or cures for many diseases, scientists are still pursuing
other ways to improve treatment and understanding of these conditions. Basic
research uncovers fundamentals of how a given biological system works, which
provides new targets for intervening, new insight into how current drugs work
or new ways to improve upon them. The more targets, the better.
What about the ethics of cell engineering and stem cell research?
At this stage of the research, ethical issues surrounding cell engineering
and stem cell research generally involve the source of the stem cells. A heated
political debate in 2001 culminated in President George W. Bush's announcement
that federal funding would be permitted only for those embryonic stem cell
lines in existence at the time of his speech (9 p.m. Eastern time, Aug. 9,
2001), since any embryos would have already been destroyed in the creation
of those lines. But the use of embryos or fetal tissue is not the only source
of ethical quandary in stem cell research. As the work approaches pre-clinical
and clinical stages in the coming years, new questions will pop up. As proved
by the "last minute" discussion on the question of federal funding,
it will behoove policy makers, scientists and the public to be prepared to
address these issues before the research they involve is a reality.
Members of the Institute for Cell Engineering and others at Hopkins have access
to bioethics consultation from experts in the Johns
Hopkins Berman Institute of Bioethics. Among other endeavors, the Bioethics Institute has established
a new program to explore the need for and creation of policy options for guiding
decisions about research with human stem cells and engineering of human cells.
The Program in Cellular Engineering, Ethics and Policy will examine the "next generation" of ethics questions in stem cell research
through its initial project, which is funded by a grant from the Greenwall
Foundation to the Bioethics Institute.
Genetic engineering, which is one way cells can be manipulated, also creates
ethical issues. In early 2002, the Bioethics Institute received a $9.9 million
grant to launch the Genetics and Public Policy Center, located in Washington,
D.C. Others at Johns Hopkins also study the ethics of applications of genetics
and offer options for the resolution of those issues, in addition to consultation
to Hopkins researchers.
What cells are being used by ICE scientists?
Researchers within and affiliated with ICE are free to use any type of stem
cell line they choose for their research, provided any necessary approvals
(for federal funding or for human subjects or animal research protocols) are
obtained. Hopkins scientists are studying human embryonic germ cells (which
were initially developed at Hopkins by John D. Gearhart's laboratory), human
embryonic stem cells, human "adult" stem cells and the corresponding
cells from mice and other animals. ICE scientists are also working with fully
differentiated cell types and studying and developing various animal models
of human disease.
How is human stem cell research regulated?
The federal government has instituted regulations for federal funding for
pluripotent stem cells from both embryos and fetuses. Research projects using
embryonic stem cells, which are from embryos, must comply with President George
W. Bush's Aug. 9, 2001, decision limiting federal funding to lines in existence
before 9 p.m. that night, and must pass review by a special committee established
to consider these proposals in addition to the standard National Institutes
of Health grant review process. Research with embryonic germ cells (derived
from fetuses) is subject to NIH policies developed during the Clinton administration.
For additional information on the federal regulations regarding stem cell
research, visit the National Institutes of Health website and for further information
on fetal-tissue-derived stem cells see http://www.nih.gov/news/stemcell/
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