You may have seen some recent headlines about pig heart or pig kidney transplants into humans. You might be curious as to how it works.
This video will provide you with an overview of xenotransplantation, otherwise known as cross species transplantation, and use case studies
to demonstrate what it’s all about!
In some diseases, one end result is organ failure. One example is heart attack which can result in heart failure. The heart is crucial to our survival
so the best treatment option is to have an organ transplant, in which doctors surgically remove a healthy heart from one person (the donor)
and place it in the individual with the weak or failing organ (the recipient).
The problem is, there is not always enough supply to meet the demand for human organs.
Many people are left waiting on waiting lists for receiving transplants. According to the US Government, more than 113,000 candidates were
on the transplant waiting list as of January 2019, while only 36,528 transplants were performed in 2018.
Xenotransplantation can help address the issue of organ shortage. If we expand our source for organs, we can provide transplants for more
people on these lists, or even people who are ineligible for transplants.
How does cross-species transplantation work? The WHO organization describes it as any case in which either cell, tissues, or organs from an animal source
are transplanted into humans. But, we can’t use any animal for this process because the body’s immune system could recognize the organ
as “foreign” and reject it, or the organ might just not be suitable for our needs.
Now we will discuss instances where xenotransplantation has been implemented on humans.
In December of last year, David Bennett, a 57 year old male, was admitted to the hospital after being diagnosed with life threatening arrhythmia.
This condition affects the heart and results in irregular heartbeat.
David’s arrhythmia meant that he was ineligible for an artificial heart pump. Plus, he was not a candidate for a human heart transplant list.
Given the severity of his situation, David agreed to have a pig heart transplant.
This procedure was not easy though. Bennett’s body could reject the pig’s organ. To overcome this, the researchers did two main things:
First, they performed genetic modifications on the pig’s heart. They knocked out 4 pig genes and added 6 human genes to the pig’s heart.
Then, they had to make sure that his body’s immune system would not attack the new organ. So, researchers developed an immune suppressing drug to prevent organ rejection.
Do keep in mind that this procedure was only possible after almost 30 years of research in the area of cross-species transplantation.
6 days following the surgery, Bennett’s body showed no signs of rejection! Doctors recommended a rehabilitation process that is similar to
that of patients receiving human transplants.
Our next case study is the recent kidney xenotransplant of James Parsons. James was a 57 year old male who suffered head trauma after an accident
and was declared brain dead shortly after. His family was approached by researchers from the University of Alabama Birmingham to discuss the potential
of a kidney xenotransplant to understand the effects of the surgery and they agreed. The study and transplant began on September 30, 2021.
The surgery had three phases beginning first with the pre-transplant stage. This took 19 hours and involved getting the genetically modified pig kidneys,
removing the participants' kidneys, and studying the anatomy of both sets of kidneys through a microscope. James had moderate acute kidney injury
due to the accident. The pig kidneys had 10 genetic modifications which will be discussed later on and were declared free of several pathogenic viruses.
The next phase was the transplant stage which only took 4 hours. Both pig kidneys were transplanted into James. Visual assessment revealed that
blood flow quickly returned to the transplanted kidneys. A drug regiment was immediately started post surgery to minimize the human body rejecting the kidney.
The final phase was the post-transplant stage which lasted a total of 74 hours. James’ immune system was suppressed over 3 days using several drugs.
He was kept in the operating room under intensive nursing care and monitoring to collect data. Both kidneys were assessed and it was determined
that the left kidney did not function as well as the right. James slowly developed multi-system organ failure due to his injuries from the accident.
The researchers ended the study once the injuries became too severe. The transplanted pig kidneys were then removed from James’ body and
inspected for signs of damage.
What exactly was so significant about this study? It was the first published/peer-reviewed study to establish brain death as a possible preclinical human model.
The study also helped us answer some important questions in the field of xenotransplantation: Would there be immediate rejection of the pig organ?
There was not. Would pig cells be detected in the recipient's blood? They were not. Could the pig kidney xenotransplantation be safely performed
under the conditions necessary for clinical trial? Yes. Would a life-threatening complication arise during the transplantation of the pig kidney?
It did not. This study allowed researchers to study the feasibility of pig kidney xenotransplantation and how to improve the practice in future studies.
To make pig organs more suitable for transplantation, 10 genetic modifications were conducted on the pig heart and pig kidneys. Six human genes
were inserted into the pig organs. The inserted human genes had two roles: reduced the chance of excessive blood clotting and reduced the risk of organ rejection.
Four pig genes were deleted in order to convert the pig’s blood type into a universally acceptable one.
In both case studies, modified pig organs were used in the transplant. Why is this? Shouldn’t we use primates, with whom we share a close
evolutionary relationship with? In 1963, a surgeon at Tulane University transplanted chimpanzee kidneys into 13 kidney disease patients.
Despite the close relationship between chimpanzees and humans, no patient survived for more than nine months, and nearly all died within weeks.
Primate kidneys are not a good fit for humans.
In the 1980s, there was a proposal that pigs could be a better source for xenotransplants. The size of pig organs closely matches those of humans
whereas non-human primates have smaller sized organs compared to humans. The use of pig organs for transplantation to humans appears closer now
aided by advancements in gene editing and transplant technique.
These case studies and recent breakthroughs demonstrate promising advancements in the field of xenotransplantation. As we further develop this technique,
we can continue to address the problem of organ shortages in healthcare. Thank you for tuning in.