Exploring the Potential of Xenografting to Transgenic Animals: Advancement,

Challenges, and Ethical Consideration

Application
People all around the world are living longer because of better medical care and
improved standards of living. Despite this, living longer comes with a higher incidence of
cell, tissue or organ loss of function or failure. This has led to new areas in medicine
such as transplants and most recently regenerative medicine. Xenotransplantation is a
medical procedure in which organs, tissues or cells from one species are transplanted
into another species, usually a human. This holds the key to changing the face of organ
transplantation and resolving its critical shortage. Only organs, tissues or cells can be
moved between different species using xenotransplantation. To accomplish this,
scientists genetically modify animals to create organs that are more compatible with the
recipient. These genetically modified animals are called transgenic animals. Organs or
tissues from these animals can then be used for transplantation into humans, potentially
saving lives and improving health outcomes. However, many scientific and ethical
challenges still need to be resolved before xenotransplantation becomes widely
available.

According to the Biotech Innovation Organization (n.d.), Human organ transplantation is

a comparatively new branch of medicine that has found itself in a dire strait. Demand for
this procedure far exceeds the availability of donor organs due to its clinical success.
The United States (U.S), however, had more than 60,000 individuals enrolled on
transplant waiting lists by end of 1998. On average, less than half of the people on
these lists are transplanted with solid organs each year. In fact ten individuals die every
day as they wait for viable organs to be donated for their survival. Furthermore, these
figures do not take into account an unknown number of people who would have been
disqualified from having such operations done because of either age or health
problems. The need for organ transplants will continue to rise as improved surgical
technique and anti-rejection drugs make it possible for some groups that were once
considered too sick e.g., diabetic patients to benefit from this option. Additionally, there
are several other diseases such as diabetes, Parkinson's disease Huntington’s disease
cancer and injury to the spinal cord or other body parts where transplanting cells or
tissues may offer benefits to numerous others. Which one of the reason why
xenotransplantation exist, to address the shortage of organs for transplantation. And
pig's organ are considered as most ideal organ xenograft donor because their organ
size, physiological metabolism and immune system are similar to those of human
beings. Also, the pig's organs are of the same anatomical character as human ones and
pigs come in all sizes. In addition, pigs have a lot of litters and are easy to breed. Since
millions of pigs are slaughtered annually for human consumption, there could be no
ethical objection to using pigs' organs for treating human disease. The fact that pigs
were suitable for genetic engineering was also a factor.
This are the tissues and organs thay can be used for xenotransplantation (Ekser et al,
2012)

EXAMPLE OF XENOGRAFTING

•PIG TO HUMAN KIDNEY TRANSPLANT

Researchers have made multiple attempts to transplant animal organs to human.
However, they have been able to genetically engineer pig kidneys that can co-exist with
the human immune system. Because according to researchers pigs are the most
promising animal kidney donor sources. The procedure they conducted for this
transplant— They started with transgenic pigs with 10 gene edits, three deletions
disable genes that would trigger the human immune system and cause rejection.
On the other hand, scientists have managed to reduced the risk of rejection but not
eliminate it completely. Then, a fourth deletion prevents the kidneys from growing too
large in the recipient. After transplant the rest human genes added to the pig genome to
prevent the human body's defenses from attacking the organ. The UAB team designed
and performed the first test to ensure both tissue compatibility of the two different
species and they confirmed there were no viruses transmitted.
Anatomically, a kidney from a genetically altered pig has been transplanted into a
real person for the first time. It took four hours at Massachusetts General Hospital on
Saturday for Richard Slayman, 62, of Weymouth, Massachusetts, who has end-stage
renal disease, to get the transplant. He's making a full recovery.
•PIG TO HUMAN HEART TRANSPLANT
While it might be accentric that an organ from a different species could function
properly to other species, scientists discovered a 98% DNA match between humans
and pigs. As stated by researchers, pigs lead to have a very similar size anatomy and
functions human heart are quite compatible.
As a matter of fact, both heart contains four chamber consisting of two ventricles and
two artia. There are also four valves that are consistent with valves in the human heart,
and aorta is in similar position. These similarities allow blood to flow through a pig heart
same way it flows through human heart. But there are also some key differences: The
shape of the pigs heart is a typical valentine heart shape, pumps horizontally since they
are four legged species, pigs recieves only two pulmonary veins. Meanwhile, human
heart is more of a trapeziodal shape, pumps vertically since human stands upright, and
left atrium receives four pulmonary veins. Lastly, both beat rate differs from each other
and must be corrected.
To surpass the mechanism of rejection, doctors administer immunosuppressive drugs
to patient. These drugs surpress the human immune system to prevent it from being
able to have a strong response against the transplanted organs. And scientists have
been devising to modify donor's genome to avoid rejection. In an working room at the
College of Maryland Restorative Center on September 20, 2023, specialists exchange
the genetically-modified pig heart to the agent field for transplant.
ADVANTAGE AND DISADVANTAGES OF XENOGRAFTING

•ADVANTAGES
>Significant savings in time
>Availability of donor organs
>Research opportunities
>Ends shortage with organ transplantion
>Models can be reproduced easily
>Compatibility with certain organ
>Considered adequate as a preclinical test of anti-cancer drugs

•DISADVANTAGES
>Carry risk of harming the patient
>Can cause infection
>Transmission of diseases
>Ethical concern
>limited lifespan of grafts
>Immune rejection
>It will take a period of time to fully be used

References

FDA.Gov. Xenotransplantation (n.d.)

https://www.fda.gov/vaccines-blood-biologics/xenotransplantation

Biotechnology Innovation Organization. Xenotransplantation (n.d.) Archive. Bio. Org.

Available at:https://archive.bio.org/articles/xenotransplantation-benefits-and-risks-
special-organ-transplantation

Groth, C.G. The potential advantages of transplanting organs from pig to man: A
transplant Surgeon's view (2007) PubMed Central®. Available at :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721611/#:~:text=Pig%20organs%20are
%20anatomically%20similar,organs%20for%20treating%20human%20disease.

Ekser, B., Ezzelarab, M., Hara, H., van der Windt, D. J., Wijkstrom, M., Bottino, R., et al.
(2012). Clinical xenotransplantation: The next medical revolution? Lancet 379 (9816),
672–683. doi:10.1016/ S0140-6736(11)61091-X

Xenografts Services. Applications of Xenografting |Scientific Applications of Xenografts

(2023) www.xenograft.net. Available at:
https://www.xenograft.net/applications/#:~:text=Xenograft%20Models%20and%20Their
%20Advantages&text=Fast%20results-,Inexpensive,the%20administration%20of
%20test%20therapies
Liu, Y., Wu, W., Cai, C. et al. Patient-derived xenograft models in cancer therapy:
technologies and applications. Sig Transduct Target Ther 8, 160 (2023).
https://doi.org/10.1038/s41392-023-01419-2

Lewis. T. Milestone Pig-to-Human Heart Transplant May Pave the Way for Broader Trial
(2023). Scientific American. Available at:
https://www.scientificamerican.com/article/milestone-pig-to-human-heart-transplant-
may-pave-the-way-for-broader-trial/#:~:text=5%20min%20read-,Milestone%20Pig
%2Dto%2DHuman%20Heart%20Transplant%20May%20Pave,the%20Way%20for
%20Broader%20Trial&text=In%20an%20operating%20room%20at,the%20operative
%20field%20for%20transplant.

Mallapaty. S. & Kozlov. M. First pig kidney transplant in a person: what it means for the
future (2024). Nature. Available at:
https://www.nature.com/articles/d41586-024-00879-y