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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 different areas of advances in transplantation including tolerance induction, bioengineering, biological markers, regenerative medicine, and artificial intelligence (Al). 

Engineering Tissues and Organs

The cells in the body create the tissue that make up our organs. The scaffold of each organ and tissue is the structure that the cells replicate on to create the fully formed and functioning tissue. And bioreactors are the chambers in which these components, combined with necessary regulatory factors that facilitate nutrient and oxygen availability to allow the cells to function, are combined to engineer new living tissue. 

With this understanding, researchers tried to create an anatomically correct jaw bone in a pig. First, they removed the bone, cleansed it of all cells and living tissue, which left the scaffold. Then they took stem cells from bone marrow tissue or fat tissue of the pig and added it to a bioreactor culture and the scaffold. After a few weeks, it became living bone. Then, this bioengineered bone was placed back into the pig to see how it integrated with the native bone over time. Over the span of 6 months, the bioengineered tissue and the naïve bone were nearly identical. 

In the human body, engineering tissues like whole organs is vastly more complicated. The lung, for example, has more than 50 cell types and a complex structure of airways and vasculature. There are 145 meters of gas exchange surface, which is half of a tennis court. With current technology and innovation, it’s not possible to engineer lungs, yet. 

But, because of the shortage of organs that are suitable for transplant, instead of growing new organs, trying to repair organs that are rejected is the near-term future of transplant innovation and research.  

This very intervention is being researched in lung transplant where the lung is placed on a ventilator and connected to the organ recipient’s blood flow for a few days to complete lung repair before it is put into the recipient patient. To test this, studies were conducted on weakened lungs that were out of the body for a considerable time, which leads to damage from blood loss. These lungs were connected to the patient externally using the method of rehabilitating the lung and after 24 hours the function of the lung dramatically improved. To determine the health of the lung, the pressure volume in the lung is tested to ascertain the quantity of much air flow.

Immune Tolerance

The immune system recognizes what is part of our body and what is not. There are proteins and carbohydrates on the surface of the organs of other people’s bodies that our immune system recognizes and tries to fight off when an organ is placed in the body for transplant. Research is being devoted into trying to reprogram our immune system so it doesn’t attack the transplanted organ and only attacks bacteria and viruses as it normally should. This is called immune tolerance. 

So, how does immune tolerance work? Our bone marrow determines what is recognized as foreign and what is not. When we are born, the immune system hasn’t created immune memory yet, which is required to remember infections we have been exposed to so they can be fought off quicker in the future. These memory cells have to be reprogrammed to not have immune recognition and then reject the organ. To do this, bone marrow cells of the donor can be transplanted along with the transplanted organ into the recipient to minimize this immune recognition of a foreign body. Those unique proteins and carbohydrates from the donor are now part of the recipient’s body and will not reject. 

In kidney transplant, there have been some studies done where kidney and bone marrow transplant were done together. Patients were able to stop immune suppression over time and they all developed immune tolerance.  

Liver transplant is the most effective organ to transplant that will create spontaneous immune tolerance as this is where bone marrow stem cells survive. Research is also looking at what are the cells and inflammatory markers that are characteristic of people that don’t reject their organs. Hopefully, this can be translated to other organs in the future. 

AI and Transplantation

There is technology being used that can predict future organ rejection. This AI technology is called AlloSure – a marker of donor organ injury and rejection. It is being developed to be used for all organ transplants, and currently is used in determining transplanted kidney health and function. Data is collected from the following results added together to predict, with 85% accuracy, if a patient will experience rejection present on a biopsy: kidney function at the time of biopsy, data history of rejection, antibodies against donor and DNA. The score determines whether the patient should be biopsied or not. A low value indicates a low probability of rejection, and a higher value where rejection is likely.

This technology would be used any time after the first 2 months and then quarterly after the first year.  Data is collected every year after transplant to predict long term outcomes of transplantation. In addition, there will be less need for conducting long term trials in the future for new drugs and interventions as outcomes can be accurately predicted. 

With advances in improving the shortage of lung supply, increasing regulatory collaboration, and improved transplant drugs, the future of transplant is bright!

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. Vunjak-Novakovic, Professor of Biomedical Engineering and Medical Sciences at Columbia University 
  • Dr. Griesemer, Professor of Surgery and Transplantation at Columbia, Head of Pediatric Renal and Liver Transplant.
  • Dr. Srinivas, VP of Digital Development and Clinical Integration at CareDx

Moderators