THE APPLICATION OF STEM
CELLS IN THE TREATMENT OF OSTEOARTHRITIS
BY
Amelia Adams Davies
(Pass with Distinction – 85%)
RESEARCH PAPER
BASED ON
PATHOLOGY LECTURES
AT MEDLINK 2011
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ABSTRACT
Osteoarthritis (OA) is by far the most common joint disease with at least 8 million sufferers
across the UK. Advances in tissue engineering and regenerative medicine brings the possibility of
the use of Mesenchymal stem cells (MSCs) for the repair of the articular cartilage and the bone in
the joint affected by Osteoarthritis. This paper will explore the possible uses and applications of
these stem cells in the treatment of OA, as well as describing the advantages and limitation of
using MSCs for the treatment of this disease. I will discuss three possible treatments for OA
using stem cells.
INTRODUCTION
Osteoarthritis is a joint disease resulting from
the damage of the articular cartilage that leads
to symptoms such as inflammation, pain, stiffness
and loss of mobility. It is characterized by
degeneration of articular cartilage, inflammation
of the synovium, the occurrence of osteophytes
and bone angulation.
As you can see from Fig. 1 and 2, OA causes the
articular cartilage and the bone to wear away,
Fig. 1 A healthy knee
causing friction between the bones. A review on
OA conducted by Goldring (2007) stated that ‘A
majority of individuals over the age of 65 have
radiographic
and/or
clinical evidence
of
Osteoarthritis’. This shows that OA is an issue
for many people today, causing people to live with
a lower quality of life because of the inability to
move without pain.
As told by Ahmed (2007), Articular cartilage distributes Fig.2 A knee affected by OA
applied load to the subchondral bone in joints and provides,
along with the synovial fluid, a low friction surface between the two bones. Adult
cartilage has a limited ability to repair and grow back after damage from an injury or
through ‘wear and tear’ by OA. A number of explanations have been put forward to
explain this, for example the chondrocytes may not be able to move to the damaged area
because of the dense matrix around the cartilage. Due to the stem cells not being able
to get to the damaged area of the articular cartilage easily, the cartilage cannot be
repair itself as quickly and efficiently, leaving areas of thin or no articular cartilage
which then leads onto OA.
Mesenchymal stem cells (MSCs) have the ability to self-renew and intrinsically repair
and regenerate damaged tissue. MSCs are adult stem cells and so are multipotent,
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meaning they have been partially differentiated into a broad cell type. They have been
found to differentiate into cartilage, bone, tendon, fat tissue and muscle cells
demonstrated by the work of Redman (2005). This suggests that MSCs would be good
for tissue regeneration, especially in joints.
There has been a great deal of research by various
academics into the use of MSCs in procedures such as
Autologous bone Marrow-Derived Mesenchymal Stem cells
implantation, such as Nejadnik (2010). This research shows
that MSCs can be differentiated into cartilage and then
implanted, as a graft, onto a damaged area of the articular
cartilage. The results for this procedure are similar to
that of Autologous Chondrocyte implantation (ACI). Fig.3
shows a chondrocyte graft onto the articular cartilage in the
knee. MSCs could be used instead of the chondrocytes for
this procedure.
Fig.3 ACI graft
At the Institute for Regenerative Medicine at the University of Pittsburgh, Dr. Gerlach
has developed the technique of putting stem cells directly onto a burn wound. Here the
cells differentiate into new skin cells to replace the dead tissue. This treatment for
burns victims is fast and although in early trails seems to be very effective for seconddegree burns. This treatment gives the possibility that different types of stem cells
could be used in this way to treat other accident/ diseases.
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DISCUSSION
POTENTIAL APPLICATION OF STEM CELLS - 1
There are many possibilities for the use of stem cells
in future medicine, including the treatment of OA.
MSCs seem to be the most useful type of stem cells
for this treatment because they differentiate into
most tissues in a joint.
Fig 4.
Fig.4 shows damage to the articular cartilage
(circled). The first possible future application of stem
cells could be to repair damaged articular cartilage
like the cartilage shown in Fig 4.
It has been shown in the treatment of burns, as described in my introduction, that
specific stem cells put directly onto damaged tissue can repair the area by
differentiating into the required tissue, replacing the damaged tissue. MSCs have the
potential to differentiate into cartilage. This means that to treat articular cartilage
damage from OA or injury, the stem cells could be injected directly into the joint onto
the affected area.
It is known that there are stem cells in joints already, however they cannot move easily
to the affected area because of various reasons. This treatment would allow the
affected area to be targeted directly. The joint matrix would then help the stem cells
differentiate into cartilage cells replacing the damaged tissue. The cartilage would then
be fully repaired and act as a healthy joint again, causing little or no pain. The MSCs
needed for this procedure could be harvested from the patient’s bone marrow under
local anaesthetic. This would mean that the stem cells used would be from the patient
and so there would be no problems with rejection (the body thinking the stem cells were
foreign and trying to destroy them).
ADVANTAGES
There would be many benefits to this type of
treatment such as its easily application. This
means there would be no need for open knee
surgery, such as in treatments like ACI and
knee replacements. Open knee surgery also
leaves a lot of scar tissue, as shown in Fig. 5,
which is not as flexible as healthy skin and so it
is harder to bend down and kneel after such
operations. However this would not happen with
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Fig. 5
injecting the stem cells, as no skin would ever be cut.
Treatments for OA at the moment mostly have long recovery time; this can affect the
person’s life, for example their ability to work for a long period of time, however if
inserting stem cells into the joint had a recovery time as short as when the stem cells
applied to the skin did, then it would mean that people would be able to carry on there
normal lives shortly after the procedure.
Other benefits of this treatment would be how MSCs are easily collected from the bone
marrow, unlike with ACI where a sufficient number of chondrocytes is difficult to
collect. This means that the MSCs can be harvested in sufficient amounts.
DISADVANTAGES
On the other hand since I have only thought of this theoretically, there may be
problems with this procedure. I will discuss the possibilities below:
The stem cells may overgrow when inserted into the knee. This means that the knee
would lock because the articular cartilage on both bones could fuse. This would be a
problem, as it would make the joint useless, however if the stem cells were injected in
small quantities this should not cause a problem. If a barrier could be made between the
two bones during this procedure, then the stem cells could differentiate into cartilage
cells to repair the damage without fusing with the cartilage cells on the other side of
the joint. A material that stops cells growing could be use for this. The material could be
inserted arthroscopically into the knee. This could be done in the same manner as stents
are inserted into arteries.
Another problem which may occur is that the matrix in the knee would not be able to
differentiate the cells into the cartilage or that they would differentiate the stem cells
into another type of cells. To overcome this, another matrix could be inserted into the
knee along with the stem cells. Nevertheless this could have an effect on the knee
itself, so careful research into the appropriate differentiating matrix would be needed.
POTENTIAL APPLICATION OF STEM CELLS – 2
In some cases of OA, the bone is also worn away, shown in Fig. 2. Osteophytes, which
are bony spurs, form because the bone is unable to grow upwards. The only effective
treatment for this is a knee replacement; cartilage grafts cannot help in this situation
because of the bone being out of shape. Joint replacements do not last forever. There
can also be other complications with joint replacements such as infection, which in a few
cases leads to further surgery to cure it. Joint replacements can also fracture the
bones around the joint or cause excess bone to form.
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In July 2011, the first synthetic organ was implanted
into a cancer patient. The trachea (Fig 6.), grown from
the patient’s own stem cells, was grown on a scaffold to
help form the shape, as shown by the growing of the
trachea, complex cell arrangements can be achieved by
differentiating stem cells.
Since MSCs can differentiate into bone and cartilage,
they could be used to grow a knee replacement using a
scaffold. The cells would grow to create a new joint,
Fig. 6
including articular cartilage and the different layers of bone. An operation
would then replace the damaged knee with the ‘new’ knee made from stem
cells. The stem cell knee replacement would be the same shape as a normal metal
replacement, meaning it would fit into the other bone. Although the advantage of this
replacement would be that after time the replacement and bone would fuse together,
creating a completely new ‘natural’ knee.
ADVANTAGES
There would be advantages to using this ‘natural knee’ replacement as it should act like
a young knee and self-renew the cartilage etc. This theoretically means that this
replacement would last longer, as it looks after itself. This would also mean that young
people who damage there knees in accidents, could have knee replacements that could
potentially last them there whole lifetime, rather than having several knee replacements
in there life.
A small percentage of people who have a metal joint replacement can have their body
reject the joint, and so their white blood cells would attack it. This would not happen if
stem cells from the patient were used, so this risk would be eliminated. MSCs are also
easily collected from the bone marrow. This would mean that the stem cells used to grow
the new joint would be readily available in large numbers.
DISADVANTAGES
The stem cells, to be able to grow to form a knee, would have to have a scaffold. To
construct this in the first place would be difficult, however once it was made this could
then be used as a template for other scaffolds. The patient would have to be taken into
consideration for the scaffold as well, as everyone has variations in knee size. This
means that all the scaffolds made would have to be custom to the patient. This would be
very expensive and time consuming. Although there are computer programmes today
advanced enough to design the scaffold itself by using a scan of the patient or
dimensions. This would mean that scaffolds could be produced more easily.
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CONCLUSION
OA is the most common joint disorder, making it important to find a treatment for it as
so many people suffer from the disease. There are so many possible uses of stem cells in
treatments in the future. In this paper I have highlighted two possible applications of
stem cells to treat OA. One would be the possible treatment of articular cartilage by
injecting stem cells directly onto the damaged area of the knee and the other would be
the use of stem cells to grow a joint replacement (e.g Knee replacement).
There are disadvantages to repairing the joint with stem cells, for example when the
stem cells differentiate into the tissue cells needed for the procedure and are applied,
the new cartilage may not be as strong and as hardwearing as the original articular
cartilage. This means that the new cartilage may just fail to function as a normal knee,
because of not being able to withstand the mechanical demands that are needed.
In this paper I have only looked into the repair of the cartilage and the bone using stem
cells, but to treat OA the contribution of the synovial fluid inflammation must also be
addressed. This means that the treatments that I have discussed may not treat OA
fully because they do not take into account the affect that the inflamed synovial fluid
has on the joint. Inflammation of the synovial fluid would be an area that in future
developments should be addressed.
In the future, OA may be treated easily by stem cells, however a lot of research is
needed into stem cells before that will be possible. The main challenge for scientist is to
find the correct differentiating matrix for stem cells so that they differentiate into
the right cell needed for that procedure. This applies to my potential procedure of
injecting the stem cells into the knee and allowing them to differentiate in situ. There
must also be a lot of scientific research into the use of scaffolds to culture stem cells
to form organs as well as structures such as joints.
Hopefully in the near future, procedures such as the ones described in this paper will be
widely available in the UK and across the world.
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REFERENCES:
Goldring M. B. and Goldring S. R. (2007) Osteoarthritis, Journal of Cellular Physiology,
DO1 10.1002/JCP 626-633
Nejadnik H. (2010) Autologous Bone Marrow-Derived Mesenchymal Stem Cells Versus
Autologous Chondrocyte Implantation: An Observational Cohort Study, The American
Journal of Sports Medicine, Vol. 38, No. 6, 2010, pages 1110-1116
Ahmed N. (2007) Mesenchymal stem and progenitor cells for cartilage repair. Skeletal
Radiol, Vol 36, pages 909-912
Redman S. N. (2005) Current Strategies for Articular Cartilage Repair, European Cells
and Materials, Vol. 9, pages 23-32
Spray-on stem cells aid burns victim, article by CBCnews,
http://www.cbc.ca/news/health/story/2011/02/04/skin-spray-burns.html
NHS Choises (2010) ‘Health A-Z – Osteaarthritis’ Teatment.
http://www.nhs.uk/Conditions/Osteoarthritis/Pages/treatment.aspx [Accessed on 7
Febuary 2012]
Arthritis Research UK (2011) ‘Arthritis information’ section. Types of arthritis –
Osteoarthritis. http://www.arthritisresearchuk.org/arthritisinformation/conditions/osteoarthritis.aspx [Accessed on 24 January 2012]
Chester Knee Clinic and Cartilage Repair Centre (2011) ‘Knee Problem – Articular
Cartilage Damage’. http://www.kneeclinic.info/problems_articular_cartilage.php
[Accessed on 26 January 2012]
Photo of scars after knee replacement. Google images,
http://www.google.co.uk/imgres?q=photo+of+scars+on+knee+from+joint+replacement&um
=1&hl=en&sa=N&biw=1280&bih=738&tbm=isch&tbnid=nkUfKz9YTN3z6M:&imgrefurl=htt
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POPSCI, article on the implantation of the first synthetic organ, 07/07/11,
http://www.popsci.com/science/article/2011-07/using-lab-grown-trachea-surgeonsconduct-worlds-first-synthetic-organ-transplant
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