FRIDAY’s “state-of-the-art” session
at the BEVA congress was opened
by Lisa Fortier of Cornell University
who posed the question:
“Regenerative therapy for equine
joint disease – where are we at?”
Regenerative therapies use
preparations made from the body itself,
known as biologics. These enhance the
body’s own potential
for healing. The
required tissue is
collected from the
injured animal, treated
to increase the desired
part of it and put back
into the patient’s site
of injury.
Three examples are
platelet-rich plasma
(PRP), autologous
conditioned serum
(ACS), and bone
marrow concentrate
(BMC).
Biologics give a
scaffold for healing
and they are a source of
cells and growth factors. The rationale
of using them is to get the injured tissue
to replace itself, rather than repair itself
by adding scar tissue. These treatments
for joints are still in development but
the experimental results are very
encouraging.
ACS was probably the first one to
be tested in horses. It seems to act by
blocking the receptor of interleukin -1
(IL-1) which is a cytokine, a soluble
protein messenger that is part of the
inflammatory process.
Experiment
In an experiment, lesions of synovitis or
early arthritis were created and ACS was
injected into the damaged joints. The
horses responded with a reduction of
lameness and synovial hyperplasia. This
effect was not seen in the placebo-
treated controls.
PRP is made by taking some of the
patient’s blood and concentrating it so
that the final platelet concentration is
between two and eight times higher than
normal.
There are several
different methods of
making PRP and so the
products differ in
volume and in their
concentration of
platelets and growth
factor.
PRP contains all the
elements of blood, about 1,500 proteins, and we do not
know the function of these taken
individually. PRP is injected into the
injured joint using ultrasound guidance.
Platelets modulate the inflammatory
response and induce blood vessel
development at the site of injury.
Fibroblasts and local stem cells are
attracted to the site and nearby uninjured cells are
stimulated to produce
autocrine growth
factor.
Bovine thrombin
can be added to the
PRP when it is being
injected or just before.
This initiates the
clotting cascade so that
the clotted PRP acts as
a scaffold for tissue
repair. Also, growth
factors are stored and
released slowly. PRP is
given in two or three
treatments a week
apart. Clinical observation established
that pain relief preceded repair.
Improving chondroprotection
Experimental PRP treatment increases
proliferation of chondrocytes and the
synthesis of proteoglycans and collagen
type 2 by the cartilage extracellular
matrix.
In cell culture, synoviocytes from
human arthritic patients cultured in PRP
gave increased hyaluronic acid
production. This suggests that PRP
could be used to improve
chondroprotection and joint lubrication.
BMC is made by centrifuging the
patient’s own bone marrow aspirate.
BMC performs better than PRP in the
regeneration of cartilage and the tissues
of the musculoskeletal system. Like
BMC it contains platelets which are a
good source of growth factors.
If it is administered in the clotted
form, it functions as a scaffold for the
regeneration. It gives better cartilage
repair than microfracture. This gain was present at 12 weeks and
eight months after the
treatment of the
experimentally-created
defects.
The regenerated
tissue was thicker, had a
smoother surface and
was more coherent with
the surrounding tissue
than the control.
Regenerative
therapies are showing great promise for
the future
treatment of
equine joint
problems but
they are still in
their youth as
regards clinical
application. Regeneration therapy needs
to be followed by a programme of
rehabilitation that is tailored to each
individual animal.
Increase exercise
Exercise needs to be increased gradually,
a 10% increase in either intensity or
duration each week is a good guideline.
Corrective shoeing and maintaining an
optimum bodyweight are also
important.
Professor Roger Smith of the RVC
outlined the use of “Bone marrow-derived stem cells for
tendon and ligament
injuries”. The aim of
regenerative medicine is
to replace the injured
tissue by tissue which is
as close as possible to
the original healthy
tissue. If left to nature,
these injuries repair by
scar tissue formation
which is less efficient in
function so the athletic
ability of the horse is
reduced and there is
high risk of re-injury.
Mesenchymal
progenitor cells (MPCs)
are good for
regenerative therapy
because they differentiate
into cell lines that lead to the formation
of new matrix.
MCPs are probably present in small
numbers in most tissues and take part in
normal repair, but by adding them in far
greater number tissue regeneration is
improved.
Bone marrow is a good source of
MCPs. This is convenient to obtain, can
be taken from the patient under
standing sedation and the multipotency
of bone-marrow derived MPCs appears
to be better than that of MPCs taken
from other sites.
Common injuries
Flexor tendon injuries in horses are
common and the nature of the lesion
lends itself to repair by regeneration
therapy. The lesion is located in the core
of the tendon, so the implanted cells are
surrounded by tendon cells.
It is also an advantage that these are highly vascularised, and at about one
month post injury, when the treatment
is carried out, the defect is filled with
granulation tissue. This acts as a scaffold
for the stem cells. The mechanical
environment is significant too, as are
local cytokines and the bone marrow
supernatant has been shown to have an
anabolic effect.
Implanting autologous MCPs
supplies the healing tendon with many
more stem cells than would be present
naturally and the tendons treated in this
manner are mechanically stronger and the treated horses are
less susceptible to re-
injury.
Full training
World-wide, over 1,500
horses have been
treated using this
method. In one analysis
which involved 113
National Hunt horses,
those horses which had
returned to full training
and had been followed
up for two years
showed a re-injury rate
of 28.9% for the stem
cell-treated horses
compared to a re-injury
rate of 56% for
conventionally-treated horses.
So, both experimentally and clinically, MCP treatment appears to be
achieving its aim of replacing injured
tendon tissue with something very
nearly as good as new both in structure
and function.
