Lyfebulb, in partnership with Columbia University, presents a virtual education series, sponsored by Veloxis Pharmaceuticals, to address key topics of living from late-stage disease through the transplantation process and beyond. Providing informative patient education is key to improving the patient experience, health communications, and health outcomes.

This session discusses three different areas of advances in transplantation including xenografts, islet cell transplants, and microbiotics. 

Xenograft

Organ supply remains the number one unmet need in transplantation. Pigs are the most appropriate donor animal for xenotransplants. These types of transplants have been performed on patients who are brain dead and cannot donate their organs. Because they are technically deceased, the FDA doesn’t weigh in on this kind of research, so the data can be used to justify future clinical trials in living humans. 

At NYU, a genetically modified pig kidney was put into such a patient to study how it would initially function in the human body. After 50 hours, there was no evidence of inflammation or rejection. In addition, two recipients received heart transplants from genetically modified pigs. Because of these recent experiments, interest has reignited for xenotransplantation, which is on the cusp of successful pig to human life-altering transplants.

So how are the pigs genetically modified? There are a number of companies that are gene editing the germ line, which means that the pigs have human genes permanently in their bodies and their offspring will as well. From this point, they can be easily bred for research purposes. They look like normal pigs; the only differences are that their cells produce some human proteins. 

Unfortunately, with xenotransplantation, there will still be need for immunosuppression therapy, because the human body has an even stronger immune response to the transplanted pig organ than another human. There is some research investigating how the immune response can also be modified genetically to reduce the response. 

Islet Transplantation

In pancreas transplantation, while the success rate is about 90%; there is risk of bleeding and other surgical complications. In order to reduce that risk, islet cell transplant was developed. This process involves taking the pancreas from the deceased donor, then taking the islet cells and infusing them into the liver of the recipient. They stay in the liver and produce insulin and modulate glucose levels. This type of transplant has been optimized for 20 years. Islets can provide long term insulin independence for patients however, immunosuppression for the patient is required.  

Researchers are attempting to develop a way to make islet cells out of embryonic stem cells to have a greater supply of cells for transplant. Some companies are engineering islets from human stem cells, but there is limited success. Islets engineered from human stem cells would provide an unlimited supply, but would require the same immunosuppression therapy as normal transplant. 

To circumvent the need for immunosuppression, using a pouch to immunoprotect the cells from the body of the recipient may avoid the need for immunosuppression. There is research being done in this space as well. 

The outcomes for islet transplant are about the same as whole pancreas transplant, with about 60% of patients being insulin independent after 5 years but, the surgery requires experience from physicians and requires patient’s adherence to be successful as any other transplant. 

Currently, the FDA has not approved islet cell transplant, so it is not reimbursable through insurance. Thus, often they are not able to be performed for patients. This issue requires legislative action to push FDA to approve islet transplant as the same as any other organ transplant to allow for insurance payments. The United States is the only country that is regulated in this way. 

Microbiotics

In intestinal transplant the microbiome in the gut has been shown to be tied to rejection episodes. The intestines are full of bacteria, both commensal (good bacteria), and pathogens, (bad bacteria). There are bacteria that are vital to our survival; some of which help us break down foods, and some release chemicals that are necessary for the body’s functioning. This ecosystem of bacteria is called the microbiome. The interplay between the microbiome and the immune system is tied because an imbalance of the microbiome can cause an increase in immune cells or T cells, causing the body to be in an inflammatory mode versus a regulatory mode. One area of recent research is trying to determine whether rejection is due to the change that occurs in the gut bacteria populations when they are introduced to the recipient’s body’s gut bacteria. 

There are immune cells that are specific to the bacteria that live in the gut and, when the immune cells die off along with the bacteria from the donor’s gut, in the recipient’s body, this can cause an imbalance and lead to rejection. This has been studied in liver transplant. 

An overall decrease in diversity of bacteria, meaning fewer different types of species, is associated with inflammation. Rejection can be potentially modulated by restoring the balance of good and bad bacteria. It must be a targeted treatment of introducing certain foods and compounds that foster the growth of certain bacteria, which can then change the body’s immune response. 

The next webinar session will focus on research into biotechnology and artificial organs with experts in the field. 

Listen to the full webinar and learn more about these conversations and further research and information about life with transplant. This, and future webinars can be found on transplantLyfe.com/webinars.  

Panelists

• Dr. Griesemer, professor of Surgery and Transplantation at NYU, Head of Pediatric Renal and Liver Transplant 
• Dr. Piotr Witkowski, Director of the Renal and Pancreas Islet Program at University of Chicago
• Dr. Joshua Weiner, Assistant Professor of Surgery at Colombia, Head of Intestinal Transplant and an expert on microbiosis

Moderators

• Mark Hardy, Professor of Surgery at Columbia University 
• Dr. Karin Hehenberger, CEO of Lyfebulb and Visiting Associate Researcher at Columbia