STEM cells seem to be the
archetypal scientific conundrum,
both an opportunity and a
challenge in waiting. Professor John
Innes has more experience than
most at both. As co-founder of the
Veterinary Tissue Bank and referral
director for CVS, he tends to ignore
the hype.
“Barely a week goes by without a
claim that stem cells are going to cure
all disease known to man, or even to
make you younger and more
attractive,” he said. “It is tempting to
get carried away with that.”
Reality is much more sobering.
“We are chipping away at the coal face
as we gradually understand more and
more about stem cells,” he explained.
“The environment is complicated
because in Europe there is a lack of
regulation of veterinary stem cell opportunities – which means people
can do whatever they like with these
therapies.”
At present “big pharma” shows
little interest in cell-based therapies.
They can neither patent the
technology nor scale it up to an off-
the-shelf therapy, leaving small
companies to scrap it out with small
budgets.
John brings some scientific method
to the discussion. What we commonly
see in therapy are adult stem cells
isolated from bone marrow or adipose
tissue. Extracts generally contain a
small proportion of stem cells (7% on
average) that can then be further
cultured and refined to increase
numbers.
This unrefined mixture is called a
stromal vascular fraction (SVF).
Autologous therapies use only the
patient’s cells while allogeneic are cells
transplanted from another donor.
“Where you get the stem cells
from will influence how well they
grow,” said John. “Another myth is
that species does not matter but we
have to study the target species.
“It looks like canine cells grow
quicker compared to human cells but
they do not respond as well to
characterised media as human cells.”
Animals as models
Animals have been used as models for
human disease for years, but the
veterinary stem cell market is well
under way.
Pioneering work done by Roger
Smith at the RVC into digital flexor
tendon therapies using mesenchymal
stem cells led to the formation of
VetCell, servicing the equine market.
The Cambridge vet school group
including Nick Jeffrey wowed human
and veterinary medics with their videos
of canine patients treated using spinal
cord therapy now walking on
treadmills after months of paralysis.
“Once people realised that these
cells had potential to form new tissue
there was an explosion of interest,”
said John.
“Early on, people looked in bone
marrow before it was realised that they
could be found in other tissues like
adipose tissue, synovium, tendon,
muscle or dental pulp.
“It was the finding that stem cells
were in adipose tissue that created
another wave of interest, because it is
easy to get to.”
Stem cell ability to regenerate is
classified from totipotent (any cell
type), through pluripotent (several
germ layer lineages) to multipotent
(cells of a single germ layer). Adipose-
derived mesenchymal cells are
multipotent. Restricted in their ability to differentiate, they
will produce cartilage,
bone, fat and fibrous
tissue.
“The major hope
from these cells was to
engineer tissues,”
explained John. “They
can certainly be
cultured using growth
factors in the lab to
form different cell
types. Tissue
engineering is an area of
active interest now
because of the thought that we might
be able to grow joints or tendons in
people.
“We have seen some delivery of
that technology to patients in a trachea
engineered for a Spanish patient. The
cartilage for that trachea was
engineered in Bristol, led by Anthony
Hollander.”
Promising data
The suspicion is that is not necessarily
how stem cells work. “It would be nice
to be able to deliver cell-based therapy
into bone to fix a non-union fracture,”
admitted John. “This is an area where
human medicine has progressed.”
At Oswestry Hospital researchers
took tibial stem cells and introduced
them to non-union fractures.
Unpublished data look promising and
case reports of similar methods in cats
need rigorous study. “The difficulty
with fractures is that you need a long
series of them to prove effect,” said
John.
Another stem
cell treatment in
knee defects is a
speciality of the
Stanmore Institute
in London.
Cultures are taken
from cartilage and
then injected back
into the knee and
sealed under a
periosteal flap.
Truthfully it is
expensive – in the region of £15,000-
£20,000.
“From studies in
animals we know they
can work and without
regulation in
veterinary medicine it
could be delivered
much more cheaply,”
said John. “It has not
been done in large
numbers in a clinical
setting because the
marketplace is quite
small.”
More importantly, there are other
difficulties to work out in
characterisation and method. Cell
preparations and growth factors
produce varying stem cell yields, cells
taken from different sites produce
varied results and patient age is a
factor. Other studies have shown that
stem cells put into arthritic joints do
not perform well.
“Rather than engineering tissue it
may be that stem cells are stimulating
other cells to change their phenotype,”
said John. “That is the kind of change
in our thinking. We are still early on
the research curve.
“Stem cell therapies hold potential
promise but also risk,” he added. “In
an unregulated environment there is
potential for loose use of language or
data and sales techniques to get
animals through the clinic door. We
have to be careful to separate the
wheat from the chaff. Equally there are
opportunities to do things much
cheaper.”
