Xenotransplantation

Xenotransplantation, the process of transplanting cells, tissues or organs

between different species, is one of the fastest growing areas of medical
research and has significant potential in solving many of the complex issues that
arise when performing and preparing transplants. However, this topic of medical
research raises many issues and is very controversial; is it ethical?
There are several advantages to xenotransxplantation when compared to
allotransplantation. With the use of animal organs, all organs will be optimal for
transplantation unlikje currently when it has become normal to accept nonoptimal human organs for transplant. This is due to there being a shortage of
human organs available. Furthermore patients would not have to wait a long
time to receive their organs and they would be available on demand. As, the
time of transplantation would be able to be prescheduled the patient would be
able to undergo pre-treatment with immunosuppressive agents. This means that
the chance of rejection would be reduced.
The first ever xenotransplantation performed on a human was in 1982, where a
baby girl with hypoplastic left heart syndrome (a rare condition where the left
ventricle is severely underdeveloped), was the recipient of a baboon heart. This
procedure was only meant to be a temporary solution to the issue, while a
replacement human heart being found. Unfortunately no heart could be found
and she died 21 days later due to graft rejection (mainly due to a mismatch of
blood types).
Current Issues of Xenotransplantation
All types of transplantation, especially xenotransplantation, carry a risk of
transferring pathogens from the donor to the patient. Whilst this issue can be
solved with pathogens by using animals that have been kept in sterile
environments, it will not work with porcine endogenous retroviruses (PERV). All
mammalian species carry these viruses as part of their genome. This means that
PERV could be transmitted by transplantation. Under normal conditions these
viruses do not cause disease, however it is believed that they could become
pathogenic when transferred into another species due to the change in
environment. An example of this was in 1990 when PERV was seen to be
transmitted from pig cells into human cells while the cell were being kept in
tissue culture. While PERV transmission has never been observed in 160
examples of pig to human xenotransplantation, patients still need to be heavily
monitored for the viruses.
So far no trials of xenotransplantation have been completely successful mainly
due to the immune response that xenotransplantation provokes in the receiving
organism. Xenotransplantation normally causes a more severe response than the
response caused by allotransplantations (inter-species transplantation) due to
the significant differences between the tissues. These rejections can occur
almost instantly and can cause death in the receiving organism within a few
hours. One of the main causes of rejection is due XNAs (xenoreactive natural

antibodies): These antibodies begin to circulate in the blood and activate the
complement system (part of the immune system that aids antibodies in clearing
pathogens from the body). This can lead to cell damage, haemorrhaging and
death in the transplanted organ. Whilst this severe response can be overcome by
using a variety of drugs and treatment, there are other more complex forms of
rejection that are not fully understood such as acute vascular rejection. The
bodys natural response means that whole organ xenotransplantations are not
currently safe and viable options and are mostly not used. Instead,
xenotransplantations are currently used for much smaller procedures such as
replacing valves within the heart using valves taken from pigs.
Future of Xenotrasnplantation and the Role of Decellularisation
Whilst direct whole organ xenotransplantations are not possible, research has
begun on applying decellularisation to make pig hearts suitable for human
transplant. Decellularisation is the process where you take an organ and you
strip it of all the cells and leave only the extracellular matrix. This would be
particularly useful for xenotransplantation as it would allow you to take the basic
structure of a pigs heart (or other organ/ blood vessel), which is very easy to
obtain and very similar to the structure of a human heart, and rebuild the heart
tissues using cells taken from the patient. This would mean that the issues of
rejection would be almost completely negated as you are transplanting the
patients own tissues. However, due to the complexity of human organs this
process is only currently available for some donor tissues such as veins. This
means that it will be potentially several decades before this procedure is
available for complex transplantations such as the heart

Image source: sciencebuzz.org

Ethics of Xenotransplantation
There are several moral and religious issues around the topic of
xenotransplantation. One of the main moral issues is the way that animals would
be treated before transplantation; they would have to be kept in a controlled,
and sterile environment before organ donation. Many people consider this cruel
and unfair on the animals, especially as they do not have the ability to give
permission. Another cause for discussion are people religious views. Many
religions consider the consumption of certain animals; pigs and cows, to go
against their religious teachings. This means that xenotransplantation would not
be appropriate in several countries and cultures.

Conclusion
Xenotransplantation is a particularly interesting area of medical research and
development, that has been proven to work on several occasions. However, as
an area of medicine it is still in its infancy and has several problems; rejection,
ethics and transfer of pathogens. These issues mean that even at the current
rate of development it could be decades before we see xenotransplantation
being used on a wide basis.