Evaluation report on the use of stem cells in the treatment of human disorders

What are Stem cells?

Stem cells are undifferentiated dividing cells that occur in embryos
and in adult tissues that require constant replacement (e.g. bone
marrow). These cells have the ability to relocate and differentiate
into specialised cells where needed (a permanent process in most
animal cells), and can regenerate infinitely. They are found in the
inner lining of the small intestine, in the skin, and in the bone
marrow. The cells become specialised because during their
development they only transcribe and translate some of the genes in
their DNA – the translated proteins modify the cell structure and
control cell processes, leading to specialisation.

Once cells have matured and specialised, they can no longer

develop into any other cells (as the cell nucleus contains the genes,
which produce different proteins and hence result in differentiated
cells being visibly different from other such cells). Therefore cells
lose their totipotency (the ability to differentiate into any body cell,
including those that will form the placenta and umbilical cord, seen
in cells such as a fertilised egg and early cells derived from the
fertilised zygote).

In addition to the adult stem cells found in the tissues of mature

organisms, stem cells also occur at the earliest stage of development
in an embryo, before the cells have undergone any specialisation.
These are called embryonic stem cells. After fertilisation, the
resultant zygote is a totipotent cell, which divides into multiple
totipotent daughter cells up to 4 times. After 4-5 days, these
totipotent cells begin to differentiate, forming a hollow ball of cells
called a blastocyst. The inner cell mass will form the animal or
human, with all these cells being pluripotent (which can specialise
any one of the cell types in a mammalian body, but can’t give rise
to an entire organism as totipotent cells can). Pluripotent cells soon
undergo further specialisation into multipotent adult stem cells,
which can give rise to a limted number of cell types (e.g. blood
cells, muscle cells, nerve cells etc.).

Due to their ability to differentiate into any other types of cell

(under certain conditions, isolated from an embryo), they can be
used to treat a variety of genetic disorders, such as the blood
disorders thalassaemia and sickle cell anaemia.
All multicellular organisms have some form of stem cell – in contrast
to stem cells found in humans and animals, plants have stem cells that
Figure 19.10 (‘Advanced Biology’ - M. b. v. Roberts)
are all totipotent (found in the ‘growing’ regions of the plant, such as
summarises the specialised cells of the immune system,
the roots and shoots). For example, if a cell is taken from the root of a
all of which originate from a stem cell in the bone
carrot and placed in a suitable nutrient medium with appropriate
marrow, which divides repeatedly with the resultant
chemical stimuli introduced at the right time, the cell will grow and
daughter cells differentiating into each cell type. All
divide into a mass of undifferentiated cells. Given the presence of
blood cells such as red/white blood cells and platelets
suitable growth factors, the cells will develop and specialise into a
are also derived from these multipotent adult stem cells
new plant organ or a complete plant depending on the growth factors
(specifically. haematopoietic stem cells). It is therefore
used. Since the new plant is genetically identical to the one from
these cells that are responsible for the repopulation of a
which the single cell came, it’s a clone. This technique is known as
person’s entire blood and immune system following a
in-vitro development, or micropropagation.
bone marrow transplant.
Where can stem cells come from for research?
Embryonic stem cells can be obtained from an embryo
created via fertilisation or cloning (somatic cell nuclear
transfer – shown opposite). The inner cell mass (ICM) of
Inset: a false-colour SEM of a single
the blastocyst of an embryo contains pluripotent cells. With stem cell
patients’ permission, researchers can obtain excess embryos Below: An infographic explaining
from in-vitro fertility clinics to isolate these embryonic
Strategies to ‘reprogram’ non-pluripotent somatic cells to becomeinduced cellular
pluripotent reprogramming
stem cells to
stem cells. produce a source of pluripotent stem
cells
Pluripotent stem cells can be derived from the primitive
germ line stem cells that exist from the blastocyst stage
until their migration to and conversion within the
developing gonads into either sperm or egg stem cells.
These cells can be obtained from terminated pregnancies,
where parents give their consent and independently end the
pregnancy. These are called primordial germ cells and have
very similar properties to pluripotent embryonic stem cells,
which can turn into any of the body’s 220 cell types.

Ooplasmic transfer is another method, which involves the

removal of the cytoplasm from an egg cell or oocyte, and
transferring it into the somatic (body) cell of a patient,
thereby transforming it into a primitive stem cell.

Parthenogenesis is a technique which appears to reduce

transplantation problems (stem cells obtained from in-vitro
fertilisation, or from foetal sources, are essentially cells
from another individual/organism – therefore if implanted
into another individual for treatment, histocompatibility is a
problem i.e. the cells would be at risk of being rejected). It
involves a woman’s egg cell being directly activated
without the removal of its DNA toEstablishing Human pluripotent
begin development on stem cell lines from embryonic or foetal tissues
its own, forming a preimplantation embryo from which
totipotent cells are isolated (a biomimetric rationale
triggering this positive response – ‘mimicking nature’).

Induced pluripotent stem cells (iPSCs) are created from

normal somatic cells (such as skin cells for example) in a
process called nuclear reprogramming. Regulator genes are
inserted (virus-mediated transfection) into the nucleus of a
skin cell, which integrate into the cell’s DNA and begin
‘reprogramming’ of the cell; cell replication results in the
creation of cells that behave very much like human
embryonic stem cells (hESCs). The use of viruses however
does make it hard to approve the use of iPSCs are
replacement cells in humans.

Adult stem cells (multipotent) and epiblast cells (cells

which share patterns of gene expression and signalling
responses similar to hESCs) are other potential sources of
stem cells. These sources avoid the ethical concerns and
controversy associated with the manipulation of human
Pluripotent
embryos to obtain cell The
stem cells. linespotential
are toolsofforexisting
both current
adult and future research, with the nuclear reprogramming of adult somatic
cells generating
stem cells for regenerative a wave isofgreat.
medicines interest
Stemin the scientific community. All of the methods used for isolating and creating
cells
pluripotent
taken from amniotic fluid,stem cells willand
the placenta be umbilical
of use in the cordstudy of stem cell biology and the development and evaluation of
therapeutic
are also promising strategies.
candidates Pluripotent cells
for musculoskeletal offer a wide range of clinical applications, particularly for the treatment of
tissue
human
engineering, and weregenetic
shown diseases
to produceandnerve
disorders.
cells, Using
liver skin cells to create stem cells should allow for therapeutic treatment to
be personalised for each patient,
cells and bone-forming cells when developed in-vitro. minimising the risk of rejection. There are many challenges associated with the
methods of obtaining the stem cells required for research – from hESCs being difficult to grow in culture and the
controversial nature of obtaining them, to spontaneous differentiation in primordial germ cells preventing pure clonal
lines, to rejection of transplanted stem cells.
How can stem cells be used? - Evaluation of
using stem cells to treat human disorders
Although there are a number of types of stem
cell in the human body, it’s the first few cells
from the division of the fertilised egg that
have the greatest potential to treat human
diseases. These embryonic stem cells can be
grown in-vitro and then induced to develop
into a wide range of different human tissues.

Potential uses of human cells produced

from stem cells
Type of cell Disease to be treated
Heart muscle cells Heart damage
Skeletal muscle cells Muscular Dystrophy
β cells of the Type 1 diabetes
pancreas
Nerve cells Parkinson’s disease,
multiple sclerosis,
(Unipotent)
strokes, paralysis,
Alzheimer’s disease
Blood cells Leukaemia, inherited
blood diseases
Skin cells Burn damage, surface
wounds
Bone cells Osteoporosis
Cartilage cells Osteoarthritis
Retina cells (eye) Macular degeneration

Some stem cell therapies already exist for

some diseases that affect the blood and
immune systems – bone marrow transplants
can be used to replace the faulty bone
marrow in patients that produce abnormal
blood cells (sufferers of diseases such as
sickle cell anaemia). The multipotent adult
mesenchymal stem cells in the bone marrow
divide and specialise to produce healthy
blood cells. This technique has been used to
successfully treat leukaemia and lymphoma,
as well as genetic diseases like severe In addition to the physical challenges
combined immunodeficiency (SCID). associated with human stem cell research
and application (some shown opposite),
The full potential of stem cells might one day there are many ethical issues surrounding
lead to non-pluripotent ‘reprogrammed’ stem cell research, particularly the use of
somatic cells able to grow into new tissue or embryonic stem cells. Currently,
an organ that the patient’s body wouldn’t embryonic stem cell research is
reject (stem cells that are genetically permitted in the UK under licence and
identical to a patient’s own cells). Scientists Inset: Diagrams showing the adultSo far, tissue
organs engineering
certain conditionshasi.e.
found success
for use in a
as a means
are trying to find ways of making multipotent and embryonic cell as key sources ofsmall number of applications such
of improving knowledge and as the repair of
adult stem cells behave like embryonic stem cartilage, and
different types of stem cell, cell culture bladder andabout
understanding trachea replacement. In
embryo
cells, raising no real ethical issues and and genetic reprogramming to induce each case, development
cells have been andisolated
seriousfrom patients
diseases,
specialisation, and the use of theseand grown
cells on material
to including scaffoldsThe
treatment. (substances used in
embryos used
reducing the restrictions in medical
treat damaged or defective tissues/regions
to support this
cell research
growth) are
in the laboratory before
produced from in-vitro
applications that they have compared to of the human body.
hESCs (ultimately aiming to produce being put back into the but
fertilisation, patient. For moreascomplex
nevertheless, the
tissues/organs when required). tissues, stem cells can be used as replacement
process leads to the destruction of ancells
due to theirembryo
ability that
to develop
could haveinto produced
tissues a
(multipotency).
foetus in the womb, there are ethical
Many believe that at the moment of fertilisation a new individual is created and hence has the
right to life, and should therefore be treated the same as a foetus or an adult human. Some even
believe that to allow this is the next step to human reproductive cloning, and that it won’t be long
before we start to use foetuses and even newborn babies for research. Therefore many believe that
adult stem cells are much more appropriate for research into the treatment of disease. Others
disagree, saying that adult stem cells (found in ‘stem cell niches’ in the body) have a limited
differentiation capacity, and typically only specialise into the cell types that make up the tissue in
which they are found.

Adult stem cells are important in medical science because they can be removed form a patient,
multiplied in culture, differentiated into the required cell types, and then transplanted back into
the same patient (therefore no immunosuppressant drugs are required – it’s an ‘autologous’
cellular medicine, compared to an ‘allogenic’ treatment involving cells from another person).
Clinical trials are underway and so many people believe this will be just as significant to society
as embryonic stem cells. Using IPSCs as alternative to embryonic stem cells (forcing somatic
cells to express key transcription factors and ‘reprogramming’ the cell) avoids the moral concerns
associated with embryos, and these cells also have very similar properties.
Supporters of human embryonic stem cell research contend that at such an early developmental
stage the embryo is just a mass of identical, undifferentiated cells, with no resemblance to a
human being or even a foetus. Scientists particularly believe that it’s morally wrong to allow
human suffering to continue when there is potential for alleviating it. As embryos are produced
for other purposes (e.g. fertility treatments) they see no reason to superfluous embryos that could
be used for research. In addition, they say that there is no guarantee that the early blastocyst stage
used for research would survive even if it never left the uterus. Yet others still say it’s wrong to
utilise embryos as a means to an end, even one as laudable as human suffering.

Public review in 2008 revealed that 60% of people surveyed supported the creation of these
embryos, provided that they lead to improved understanding of diseases – therefore a significant
40% minority strongly opposed their creation, regardless of medical potential. Often branded as
‘an offence to the dignity of humans and animals’, it appears that the controversy and difference
in opinions amongst the global population is a significant barrier to potentially further progress.
However, the decision-making process has to take into account everyone’s views regarding stem
cell research and its role in treating human disorders and diseases that are currently incurable.