At the University of Virginia Division of Transplant Surgery, we are committed to translational research, believing that the research we do in our laboratories should advance the science of transplantation and result in better outcomes for patients in our clinics.
With that goal in mind, we are partnering with researchers in the Departments of Biomedical Engineering and Electrical and Computer Engineering to improve the way islet transplants are done – and how successful they are. Islet transplants can help improve the blood glucose control of type 1 diabetics and patients with chronic pancreatitis, preventing many of the serious complications that arise from those conditions.
Here is what you need to know about our latest islet transplantation research:
- We are developing unique and novel technologies to sort islets and select the best ones to be transplanted.
The current method for isolating islets is 30 years old and doesn’t involve any sorting of islets. This results in a large amount of unhealthy islets being injected back into the patient and exacerbates the immune rejection response, ultimately limiting the effectiveness of the procedure.
By contrast, the microfluidics sorting technology that we are developing will enable us to sort the islets based on their viability and their potential engraftment ability, so that we can deliver only the most high quality islets, reduce the immune rejection response, and achieve better functional outcomes.
- Selecting the best islets means needing less pancreatic tissue – and thus being able to use tissue from living donors, making it more likely that a patient will receive the transplant they need.
At present, it takes two pancreases (donated by two organ donors) in order to get enough islets to inject back into the recipient patient. The main reason this large amount of donor tissue is required is that the processing is inefficient. It takes a long time, and there isn’t a way to separate the healthy islets from the acinar tissue (the “waste” tissue, which needs to get discarded before injection), so many healthy islets end up being thrown away.
We expect that the microfluidics-based technology we develop will enable more efficient sorting, so the amount of pancreatic tissue we need in the first place will be less.
This then leads us to the idea of harvesting pancreatic tissue from healthy donors. There is a lot of evidence to support the idea that a healthy patient could donate 25% of his/her pancreas and not even notice that they were missing this amount of tissue. The remaining 75% of their pancreas would be more than sufficient to sustain normal insulin production levels. Studies have further suggested that a patient may be able to produce a sufficient amount of insulin with only about 20% of his/her pancreas. If our microfluidics technology can enable more efficient islet harvests, then we can conceivably get enough islets from 1/4 of a healthy pancreas to be able to adequately treat a diabetic patient.
Instead of having to wait for two organ donors to show up, parents and siblings could instead donate pieces of their own pancreas to their diabetic relatives and not even miss it.
- We are working with high precision 3D bioprinters to develop encapsulation techniques that will reduce the attack response the immune system usually has after transplantation, including islet transplants.
Take a moment to imagine you have ordered a case of wine from California. First, you want to select the best bottles of wine. Then, you need to ship them across the country. During their journey, they may be jostled around in planes and trucks and sit for hours in inhospitable temperature conditions. There is a risk the bottles will be broken or the wine ruined. Careful packaging would make it more likely that they would safely arrive at their intended destination.
Now bring your attention back to islet transplantations. Current procedure is for islets to be injected in solution through a catheter that is inserted into a patient’s hepatic portal vein, the blood vessel that carries blood to the liver. We cannot be sure of where they land or whether they even survive their journey. Our goal is to use the 3D bioprinter to package the healthy islets that we have selected into protective, implantable parcels that will prevent them from being attacked by the immune system. This increases the likelihood that the islets will successfully engraft into the recipient and function at their optimal capacity.
This innovative research is a collaboration among Ken Brayman, M.D., Ph.D., of the Division of Transplant Surgery; Shayn Peirce-Cottler, Ph.D., of Biomedical Engineering; and Nathan Swami, Ph.D., of Electrical and Computer Engineering.
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Read a brief tutorial of how islet transplants work.