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A newly fertilized egg has cells that have no particular function.
Stem cells from embryos can become any kind of cell in the human body.
This article aims to describe the recent progress in stem cell research
and the likely future therapeutic applications.
The world of stem cells
We are aware that different types of cells make up our body (e.g., blood
cells, skin cells, cervical cells) but usually forget to appreciate that
all of these different cell types arose from a single cell, the
fertilised egg. Developmental biologists study the awesome events that
occur between the fertilised egg and the formation of a new individual.
The first steps simply involve cell division: one cell becomes two cells;
two cells become four cells, etc.
Each of these individual cells of early development is not specialized (undifferentiated),
that is it does not have a specific body function, and has the
capability to contribute to all of the organs in an individual and thus
are called totipotent.
These cells are embryonic stem (ES) cells and have both the capacity to
self-renew, thus maintaining a continuous supply of stem cells and the
ability to give rise to specialized (differentiated) cell types, such as
liver cells or brain cells.
It is believed that once differentiated, cells remain so and usually
lose their ability to divide.
Stem cells from adults can also be used in cell therapy, with
limitations. Stem cells also exist in adults and allow specific tissues
to regenerate throughout life. They also have the ability for
self-renewal and multi-lineage differentiation. In fact, the list for
identifying adult stem cells and lineage specific progenitor cells (with
limited self-renewal ability) is growing.
Embryos and living or dead adult tissue provide stem cells.
Sources of stem cells
The main clinical application of stem cells is as a source of donor
cells to be used to replace cells in transplantation therapy. Stem cells
can be obtained from several sources:
Spare embryos: stem cells can come from leftover embryos stored at
fertility clinics that were not used by couples to have children.
Special purpose embryos: embryos are created in vitro fertilization (artificially
in the lab) for the sole purpose of extracting their stem cells.
Cloned embryos: embryos are cloned in labs using somatic nuclear
transfer method in order to harvest their stem cells.
Aborted fetuses: stem cells are taken from fetuses in early development
that have been aborted.
Umbilical cords: this after-childbirth tissue holds potential for
research.
Adult tissue or organs: stem cells are obtained from the tissue or
organs of living adults during surgery.
Cadavers: isolation and survival of neural progenitor cells from human
post-mortem tissues (up to 20 hours after death) has been reported and
provides an additional source of human stem cells.1
Embryonic stem cells must be obtained when an embryo is in early
development, that is, when the fertilised egg has divided to form about
1000 cells. These cells are separated and maintained in a cell culture
dish, thereby halting embryonic development towards creating an
individual. This is why embryonic stem cell research is the subject of
ethical debates. Utilization of adult stem cells pose less of an ethical
dilemma: however, adult stem cells may not have the same potential as
those derived from embryos for medical therapeutics.
Embryos can contribute an endless supply of stem cells.
Comparing embryonic and adult stem cells
Embryonic stem cells have advantages and disadvantages for therapy.
Advantages: They are
Flexible: They have the potential to make any body cell.
Immortal: One cell line can potentially supply endless amounts of cells
with carefully defined characteristics.
Easily available: human embryos can be obtained from fertility clinics.
Disadvantages: They could be
Difficult to control: The method for inducing the cell type needed to
treat a particular disease must be defined and optimized .
At odds with a patient's immune system: It is possible that transplanted
cells would differ in their immune profile from that of the recipient
and so would be rejected.
Ethically controversial: Those who believe life begins at conception say
that doing research on human embryos is unethical even if donors give
their consent.
Adult stem cells also have good and difficult characteristics for
therapy.
Advantages: They are
Already somewhat specialized: Inducement may be simpler.
Immune hardy: Recipients who receive the products of their own stem
cells will not experience immune rejection.
Flexible: Adult stem cells may be used to form other tissue types.
Mixed degree of availability: Some adult stem cells are easy to harvest
and others, such as neural (brain) stem cells, can be dangerous to the
donor.
Adult stem cells are sometimes hard to obtain and don't last long.
Disadvantages: They could be
Minimal quantity: They are difficult to obtain in large quantities.
Finite: They don't live as long in a culture as embryonic stem cells.
Genetically unsuitable: The harvested stem cells may carry genetic
mutations for disease or become defective during experimentation.
Stem cells can develop into liver, heart, blood, or any other cell.
The surprising property of adult stem cells: transdifferentiation
Adult stem cells were thought to be restricted to produce differentiated
cells, which were specific to the organ from which they were isolated.
Recently, several examples have been reported which demonstrate that
these stem cells, under certain conditions, can be induced to form other
cell types (transdifferentiation). For example:
neural stem cells (NSC) can give rise to blood and skeletal muscle
bone marrow cells can give rise to muscle, liver cells, and astrocytes
Stem cells can be transplanted directly into the patient.
When NSCs were used to form muscle, no inducers were needed other than
co-culturing them with muscle progenitor cells (myoblasts) or injecting
them into muscle.2 This holds promise for cell transplantation therapies
in that the experiment suggests that host tissue can instruct
transplanted cells to a desired result. Scientists, then, can consider
whether it is best for stem cells to be differentiated in vitro (artificially)
prior to transplantation or by transplanting them directly into the
defective tissue. Some experiments have shown that naturally
transplanted stem cells were able to migrate to regions where cells had
died due to stroke (called ischaemia).
Stem cells can renew blood and bones after chemotherapy.
Stem cell therapies
Stem cells offer the opportunity of transplanting a live source for
self-regeneration. Bone marrow transplants (BMT) are a well known
clinical application of stem cell transplantation. BMT can repopulate
the marrow and restore all the different cell types of the blood after
high doses of chemotherapy and/or radiotherapy, our main defence used to
eliminate endogenous cancer cells. The isolation of additional stem and
progenitors cells is now being developed for many other clinical
applications. Several are described below.
Stem cells from hair can grow into skin.
Skin replacement
The knowledge of stem cells has made it possible for scientists to grow
skin from a patient's plucked hair. Skin (keratinocyte) stem cells
reside in the hair follicle and can be removed when a hair is plucked.3
These cells can be cultured to form an epidermal equivalent of the
patients own skin and provides tissue for an autologous graft, bypassing
the problem of rejection. It is presently being studied in clinical
trials as an alternative to surgical grafts used for venous ulcers and
burn victims.
Stem cells can provide dopamine - a chemical lacking in victims of
Parkinson's Disease.
Brain cell transplantation
Neural stem cells were only until recently thought to be strictly
embryonic. Many findings have proved this incorrect. The identification
and localisation of neural stem cells, both embryonic and adult, has
been a major focus of current research. Potential targets of neural stem
cell transplants include stroke, spinal cord injury, and
neurodegenerative diseases such as Parkinson's Disease.
Parkinson's Disease involves the loss of cells which produce the
neurotransmitter dopamine. The first double-blind study of fetal cell
transplants for Parkinson's Disease reported survival and release of
dopamine from the transplanted cells and a functional improvement of
clinical symptoms.4 However, some patients developed side effects, which
suggested that there was an oversensitization to or too much dopamine.
Although the unwanted side effects were not anticipated, the success of
the experiment at the cellular level is significant. Again, further
studies are needed and ongoing. Over 250 patients have already been
transplanted with human fetal tissue.
Several biotechnology companies are developing different strategies of
stem cell therapies.
Diacrin has been developing xenotransplants using fetal pig cells.
Clinical trials for chronic stroke patients have begun. Presently,
stroke patients require treatment within 24 hours after stroke for
effective therapeutic results. Many patients do not receive treatment in
time because the symptoms are not initially obvious. Diacrin's therapy
could be applied weeks to months after the initial trauma.
NeuroNova's strategy is to culture adult human cells from donors,
differentiate them in culture to produce the cell type (dopaminergic
neurons) which is lost in Parkinson Disease, and to transplant them into
the brain of patients.
Neurotech is using genetically altered brain endothelial cells (engineered
to produce human Interleukin-2) as immunotherapy for gliomas. Results
from experiments in rats showed that these cells "mopped up" the tumour
cells and as a result a clinical study has commenced.
Mouse stem cells were made to produce their own insulin. Treatment for
diabetes
Diabetes affects 16 million people in the U.S. and is caused by the
abnormal metabolism of insulin. Normally, insulin is produced and
secreted by the cellular structures called the islets of Langerhans in
the pancreas. Recently, insulin expressing cells from mouse stem cells
have been generated.5 In addition, the cells self assemble to form
structures, which closely resemble normal pancreatic islets and produce
insulin. Future research will need to investigate how to optimise
conditions for insulin production with the aim of providing a stem
cell-based therapy to treat diabetes to replace the constant need for
insulin injections.
Mouse brain stem cells could self-repair.
Future directions
The generation of new neurons in the adult brain is limited. However,
self-repair of neuronal cell death has been recently demonstrated in the
mouse and suggests that stem cells which normally reside in the brain
may someday be able to be stimulated by inducers in a manner similar to
how we induce our immune system by vaccination.6 This would bypass the
need for cell transplantation. Intensive research needs to be pursued
into the cell mechanisms involved.
The potential of embryonic stem cells to provide other differentiated
cell types needs to be investigated. The production of cardiac muscle
cells, which have thus far been evasive, would hold tremendous promise
for the number one killer: heart disease.
Poll: The majority of Americans favor stem cell research.
Scientists and stem cell research
Scientists believe that stem-cell research could lead to cures for a
myriad of diseases afflicting humans. Anti-abortion groups, some
religious groups, and conservative citizens say that using cells from
embryos is immoral because it destroys life. However, a recent ABCNews/Beliefnet
poll has shown that Americans support stem cell research by a 2-1 margin
and say that it should be funded by the federal government, despite
controversy over the use of human embryos.7
Conclusion: Stem cell research should be pursued but under legislative
guidance.
Most scientists Do Not support applications for human reproductive
cloning (that is, they do not want any embryos altered during stem cell
research to develop past a defined stage). They agree with governments
and concerned citizens that it should be banned worldwide. However, they
Do want the opportunity to continue stem cell research for clinical
applications under appropriate regulation and legislation with the hope
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