Medical Megatrends: Xenotransplantation –Transplanted Organs or Cells From A Pig

7 Min Read

Here is a possible medical megatrend in the making. There are many more individuals with end stage kidney failure, heart failure, chronic lung disease, or liver failure who would benefit from a transplanted kidney, heart, lung or liver than are available. Similarly, there are many people with unstable, difficult to control diabetes that could benefit from a ready source of pancreatic insulin-producing islet cells.

Here is a possible medical megatrend in the making. There are many more individuals with end stage kidney failure, heart failure, chronic lung disease, or liver failure who would benefit from a transplanted kidney, heart, lung or liver than are available. Similarly, there are many people with unstable, difficult to control diabetes that could benefit from a ready source of pancreatic insulin-producing islet cells.

Today the only option for more organs available for transplant is to encourage more individuals to pre-certify their desire for organ donation should they die in a traffic or other accident and for more individuals to volunteer to be a donor of a kidney or segment of a liver. 

But another approach, still in the future but gaining traction, is to use organs from an animal – known as xenotransplantation. 

Most research in xenotransplantation focus on the pig, in part because the organs are near to the same size as humans and the physiology is similar. Very real progress has been made in recent years. The steps required to make this approach effective include genetic modification of the pig so that the human immune system will no longer “reject” the transplanted organ. This has included removing the genes that produce the most important pig carbohydrate antigen that human immune cells recognize. Another step has been to add genes that create certain protective proteins in the complement regulatory system (another part of the body’s mechanism to eradicate “foreign” materials like bacteria, viruses or cancer.) So far, these steps have been major advances but not sufficient so further efforts will be necessary in order for say, a pig heart or kidney to be successfully transplanted into a primate and eventually into a human. 

Further progress in xenotransplantation is likely but there are significant barriers to success. Genetic modification of the pig is possible but it is not yet clear all of the modifications that will be necessary. Concurrently, work is progressing to develop immune modulation with drugs just as is done to suppress the immune system with human to human organ transplants. 

Although xenotransplantation has not progressed far enough to allow transplanting a pig organ to a human, there are other exciting opportunities in the works for xenotransplantation in the not to distant future. 

Individuals that develop liver failure often die before a suitable donor can be found or before the damaged liver can heal on its own. There is no artificial liver comparable to the dialysis machine for kidney failure. But using a specially develop pig liver outside the body to cleanse the person’s blood of noxious compounds is a possibility. There have been some positive results using a normal or a genetically modified pig liver for such “extracorporeal” perfusion until a donor organ is available or until the patient’s liver recovers on its own. Another approach is called the bioartificial liver device that uses pig liver cells suspended in fiber tubules with the patient’s plasma run through it. These have been used with some success in acute liver failure giving time for the patient’s liver to recover. 

Progress has also been made with genetically modified insulin-producing pancreas islet cells for treating diabetes. One approach is to place the transplanted islet cells into a “capsule” that allows insulin to exit out and nutrients like glucose to enter in yet keeps immune cells that would destroy the islet cells at bay outside the capsule. 

A group in New Zealand has been studying the use of islet cells derived from pigs which have not been genetically modified. The cells are encapsulated with a seaweed derived substance to protect them from immune cells while allowing oxygen and glucose in and insulin out. The company reports that they are self regulating (meaning that they will produce insulin as needed based on the body’s blood sugar levels) and efficient at secreting the insulin produced into the patient’s body. The investigators report on one patient that is now nearly 10 years since transplantation with persistent functioning islet cells. Dr John Baker and Living Cell Technologies are conducting a human trial of patients with type 1 diabetes after having tested their product in multiple animal models. The early trials will be to determine the optimal cell numbers placed into the peritoneal cavity along with safety information. For more information, check out the US National Institutes of Health Clinical Trials web site [http://tinyurl.com/2fmcnp6 ], for material prepared by the company and its investigators.The results of this study, still a few years off, will be of great interest to those whose diabetes is hard to control with standard insulin approaches.

Meanwhile expect further research to be completed on other aspects of xenotransplantation for whole organs and manipulated cells. It is an exciting time, the progress is real and the prospects, although fraught with barriers to success, are promising. Whether xenotransplantation will rise to the level of a medical megatrend is unclear but it does certainly represent exciting innovation. Stay tuned.

 


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