Download What about Artificial Organs?

What about Artificial Organs?
Path to
the future...
Mechanical Kidney
Man-made Devices
Researchers from the Kidney Project are creating a
bioartificial kidney as a permanent solution to end
stage renal disease. The implantable bioartificial
kidney builds upon the existing extracorporeal
Renal Assist Device (RAD), which is a bioartificial
kidney that combines a membrane hemofilter and
a bioreactor of human renal tubule cells to mimic
many of the metabolic, endocrine, and immunological functions of a healthy kidney.
The ultimate goal of The Kidney Project is to apply
microelectromechanical systems (MEMS) and
nanotechnology to miniaturize the extracorporeal
RAD into a surgically implantable, self-monitoring,
and self-regulating bioartificial kidney.
For many years, reseachers have
manufactured devices that are
used to diagnose, prevent, or
treat disease or other conditions
in humans. Cochlear implants,
pacemakers, ventricular assist
devices, dialysis machines and
even prosthetics, carried inside
and outside the human body, have
enabled major improvements
in quality of life and even
prevented imminent death while
awaiting a transplant.
Artificial Organs are specifically
engineered from polymers, glasses
and ceramics, nano-technology,
metals, alloys and composites or
a combination. These man made
devices are to be implanted or
integrated into a human body
to replace a dysfunctional full
organ.
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One solution for the shortage of transplantable organs is
creating artificial ones that last.
Already, researchers are developing bioartificial organs that can keep patients
with serious organ failure alive and functioning for years. For now, the goal is to
keep patients alive until they can receive a real organ, but one day, patients may
be able to live for long periods of time with artificial hearts or kidneys.
What if we could completely eliminate organ transplantation by deploying
articifial hearts and kidneys which gift a full lifespan to the recipient?
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Total Artificial Heart
For patients suffering from end-stage biventricular
heart failure in which both ventricles can no longer
pump enough blood for a person to survive, a donor
heart transplant is the standard of care. However,
not all patients waiting for a donor heart will have
one available to them when they need it to save
their lives. In the United States, approximately
16% of transplant-eligible patients on the list die
or become too sick for a transplant while waiting for
a donor heart. A manufactured full-functional
artificial heart replaces both failing ventricles and
all four heart valves. This artificial heart is deployed
as either a bridge to a matching donor heart
transplant or for permanent use for patiens who are
not transplant-eligible, also known as destination
therapy.
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HQ/TPTP/15/0010j
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What about Bioengineering
Organ Preservation?
Organs?
Path to
the future...
Organ engineering is a new
strategy to cope with the
shortage of donor organs.
The bioengineered organ will not be
rejected and there will be no need for
life-long immunosuppressant therapies.
The scaffold material does not contribute to the
rejection, and the cells that are used to repopulate the
organ scaffold belong to the patient. Patients no
longer face a lifetime filled with the need to take
immunosuppressant drugs to prevent organ rejection,
and will retain overall immune competence.
The concept is based upon the isolation
of a three-dimensional, biological scaffold
material, which has no cells in it. This
scaffold from explanted organs is prepared
by removing all cellular components
(decellularization) by washing it with a
special detergent-like mixture.
This acellular scaffold retains the native
organ ultrastructure and can be seeded
(repopulated)to generate a functional
organ in vitro for transplantation.
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The patient’s own cells are converted into stem cells
- those super-adaptable “pluripotent” cells that can
transform into virtually any other kind of cell.
The researchers take a patient’s cells, such as a skin cell or a muscle cell,
and convert it into a stem cell that can be driven along a particular line of
differentiation. This way, a stem cell can be coaxed into becoming a liver
cell, or a kidney cell, a heart cell, or whatever is required.
These cells are used to seed the 3D protein scaffold to grow a new organ.
It is pivotal to also grow the appropriate blood vessels to provide the
organ with oxygen and nutrients.
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Heart, liver, lung and kidneys.
In recent years, organs such as heart, liver,
lung and kidneys, have been reported to
provide acellular extracellular matrix
(ECM)-based scaffolds and demonstrated
the potential of recellularization with
selected cell populations, particularly with
stem cells. The current scientific need for
further studies, concerning the source of
donor organs, optimization of the
decellularization process, the cell
type for the reseeding process and the
establishment of the optimal conditions
for the repopulation of the scaffold is
still tremendous.
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HQ/TPTP/15/0010j
What about Organ Preservation?
Path to
the future...
Organ preservation is used to maintain an
organ’s viability outside the human body,
allowing more time for doctors to assess
its condition prior to transplantation.
Doctors are able to assess the quality of the organ and
investigate its anatomy to confirm whether or not an organ
meets the criteria to be transplanted.
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Will perfusion technology
ultimately ensure that all
donated organs are used?
Dr. Shaf Keshavjee, a thoracic surgeon
and director of the lung transplant
program at Toronto General Hospital,
who successfully developed a lung
perfusion machine says: “In a donation
after cardiac death, only 2% of lungs are
typically used.” “I think this could easily
be moved to 50%. We can re-use many of
the lungs we don’t use today. Now we can
see we are not only going to preserve an
organ, but we are going to make it better.
I think that this strategy is applicable to
all organs, but they have specific needs.
I think mistakes in the past have been
assuming all organs need the same thing.
So systems need to be developed to meet
the needs of each organ.”
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Organ Perfusion Systems will keep
organs alive outside the body.
Instead of cooling the organ, which slows down
the process of death, Organ Perfusion Systems
keep the organs at normal body temperature to
allow recovery from the trauma associated with
donation or as a result of chronic disease. The
Perfusion System feeds the organ with nutrients,
removes waste products, provides oxygen and
removes carbon dioxide according to the specific
organ’s needs.
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The machine not only keeps the donor
organ alive, it may even enhance the
organ by improving its condition.
By keeping the organ alive outside the body for a
couple of days, we will be able to diagnose
infections or abnormalities, and drugs can be
delivered when needed. Recovery of the organ
begins before the actual transplant starts.
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HQ/TPTP/15/0010j
What about Printing Organs?
Path to
the future...
3-D Printing also allows other body parts
and tissues to be generated such as muscle,
bone and outer-tissue body parts like ears.
We are still many years away from 3-D Printing on a routine
basis, but there is hope that organ printing could one day
supplement the shortage of live organs. Skin, blood cells, heart
valves, blood vessels and bladder are under investigation and
there are high hopes that one day we will be printing complete
organs like kidney, heart and liver. All would be printed with
the patient’s own cells, so the organ works for life.
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Researchers create a blueprint from
a patient’s organ by computerising a
CT scan of the particular organ.
All data from the CT scan is used to build a 3-D
reconstruction of both the inside and outside of
the organ, including its blood supply vessels.
Dr. Anthony Atala, a practising surgeon and director
of the Wake Forest Institute for Regenerative
Medicine:“This model is used to guide the printer
as it layer-by-layer prints a three-dimensional
structure made up of cells and the biomaterials
to hold the cells together.”
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An inkjet made my bladder.
Printers are modified in such way
that the printer sprays cells instead
of ink. By spraying layers of cells in a
biodegradable mould, both tissues and
organs can be printed for safe and
effective long term use.
Future developments will allow 3-D
printing directly onto the patient, for
instance by scanning a wound.
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HQ/TPTP/15/0010j
Will 3-D printing of replacement
tissues and organs finally put an
end to organ shortages?
Regenerative Medicine is investigating how to
replace old and poorly-functioning tissues and
organs with new and healthy tissues and organs
originating from the patient’s own cells. Some
cell types like skin or blood cells are easily
obtained from the patient’s as they are constantly
growing. Other cell types need to be grown from
stem cells recovered from the patient’s bone
marrow. Stem cells may also be derived from
amniotic fluid, placenta or umbilical cord.
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What about Growing Organs in Animals?
Path to
the future...
Will growing organs
in animals provide a
plentiful supply of
donor organs?
An exciting vision for the future
would be realised if Organ
Engineering became a substitute
for transplantation, overcoming
problems such as organ donor
shortages thus reducing or
obviating the need for
immunosuppressive therapy.
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When fully grown, the adult host animal
is put down, and the human organ will
be harvested and transplanted into the
human patient with organ failure.
Using a patient’s own stem cells could help to reduce the
risk of the transplanted organ being rejected while also
providing a plentiful supply of donor organs. Professor
Chris Mason, chair of regenerative medicine at University
College London, said: “For something like a kidney
transplant where it is not urgent, it would be highly
attractive to be able to take cells from a patient, grow
them in this way and deliver a personalised kidney.”
Researchers injected stem cells from rats
into the embryos of mice that had been
genetically altered so they could not produce their own organs, thereby creating
mice with rat organs.
Professor Hiromitsu Nakauchi, director of the centre for
stem cell biology and regenerative medicine at the
University of Tokyo in Japan: “The technique, called
blastocyst complementation, provides us with a novel
approach for organ supply. We have successfully tried it
between mice and rats. We are now rather confident in
generating functional human organs using this approach.”
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This technique could be used to introduce
human stem cells into the embryo of an animal,
most likely a pig, to create a chimeric embryo.
By using a patient’s own stem cells it will help to reduce organ
rejection. This chimeric embryo will be implanted into an animal’s
womb where it will grow into a ‘normal’ animal. As the host animal
matures into an adult, the human stem cells will grow to become a
perfect human organ such as a pancreas, kidney or a heart.
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HQ/TPTP/15/0010j
What about Self
Artificial
Monitoring?
Organs?
Path to
the future...
Dose Concentration
versus Drug Response
By improving the analytical methods and devices to
measure the low concentrations of immunosuppressants
in biological fluids, organ recipients can very easily
monitor their individual drug levels at home.
Measurement of the low drug concentrations offers the opportunity to reduce
patient variability using real concentrations in the body rather than by dose
alone. The dose of the drug can then be customized to the patient to maximise
therapeutic effect while minimising the risk of irreversible kidney damage when
given in too high a dose.
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The dose administered does not
directly correlate to the available
drug concentration in the body,
for instance due to variability in
absorption or metabolism of the
drug. Therefore, a poor relationship exists between dose
concentration and drug response.
Because of this poor relationship,
immunosuppressant drugs have
significant inter individual
variability. Even within the same
one patient, drug concentration
may vary, for example due to
drug-nutrient interaction, renal
insufficiency or inflammation.
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As some drugs have a narrow
therapeutic index, the difference
between therapeutic benefit and
toxicity is small.
Too much drug is associated with toxicity and
too little with organ rejection.
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Easy Self Monitoring could help to
increase patient survival.
As the number of immunosupressant drugs will
increase in the future, Self Monitoring will tailor
immunosuppression to the specific characteristics of
the individual patient changing dose and drugs as
time progresses and conditions change.
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What if we could obtain the optimum balance
between therapeutic efficacy and adverse and
toxic events by Self Monitoring?
How about that?
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HQ/TPTP/15/0010j