DRWF Research Manager Dr Eleanor Kennedy reports from second day of the European Pancreas and Islet Transplantation Association 10th EPITA Symposium & 39th AIDPIT Workshop in Igls, Innsbruck, Austria.
Day 2 of the 10th annual meeting of the European Pancreas and Islet Transplantation Association (EPITA) dawns in bright alpine sunshine and with a clear blue sky and everyone is in high spirits as they walk along the snowy pavements to the conference centre.
Unlike yesterday which focussed on stem cell therapies, today the talks centre around clinical graft successes and failures both for islet cell procedures and for whole pancreas transplantation.
New technology for islet cell transplantation
When it comes to islet cell transplantation, the well-recognised issues of donor organ shortages are highlighted and how these shortages will ultimately drive the exploitation of stem cell-derived islets as an alternative cell source.
In the meantime, of course, the other issue is that, once islets are made available for transplant, they still need to be protected from an immune system which has already destroyed the endogenous beta cell population in the pancreas and which will simply repeat the process.
A whole new field of technology
To do this, a whole new field of encapsulation technology has arisen to consider innovative solutions to provide an effective immunobarrier or envelope around the clusters of islets to protect them.
Within this new field, there are those who believe that multiple microencapsulation of just a very few islet cells at a time is the optimal way forward. And there are those who believe that a much larger number – macroencapsulation - is better. Either way, membrane encapsulation material needs to allow the free flow of glucose, oxygen and insulin to and from the islets whilst having a molecular exclusion capacity that protects the encapsulated islets from the cells of the immune system and humoral immune mediators.
The encapsulation barrier is just one issue – size and capacity need to be considered as does the long-term stability and functionality of the enveloped islets and the highly debated best site of implantation.
There are a raft of theoretical islet graft sites which range from the lung and the liver to the brain, the kidney capsule and the omental pouch and each research group has its preferred site!
Regardless of the site chosen, there are further additional problems to be considered. The site needs to be well vascularised with a constant, rich oxygen supply and access to representative blood glucose levels.
Importantly, the site needs to have easy access for implantation but also for explantation in case the encapsulation device needs to be rapidly removed for any reason.
Pioneering devices for islet cell transplantation
Despite all of these potential pitfalls and demands many companies are working on exactly this kind of encapsulated islet technology.
One is pioneering the transplantation of the device first in order to allow the body to create a vascularisation network several weeks ahead of the addition of the islet cells into the device.
Another, in order to overcome the high oxygen requirement that transplanted islets require, is even considering the incorporation of algal material which will photosynthesise and, thus, produce oxygen right in the proximity of the islet cells.
The old proverb says that necessity is the mother of invention so it will be interesting to see if and how these very creative potential solutions, among others, succeed!
The flip side of islet cell transplantation is whole pancreas transplantation
This procedure has a much longer history with many more people having received a solid organ transplant of this nature. But it is still not without its issues too!
One of the main factors – and this is one that affects both whole organ and islet transplant – is the speed of organ retrieval once a suitable donor has been found.
The pancreas is particularly susceptible to what is called warm ischaemia, a period of time during organ harvest when the amount of oxygen getting to the pancreas is decreasing.
This has an enormous impact on the viability of the organ for transplant so surgical teams need to be aware of this. But, their haste to get the pancreas removed from the donor has to be carefully balanced against attention to detail to avoid any damage to the pancreas.
Since this damage is common and leads to either a failure to graft or a complete loss of the organ before any transplant procedure, there is a rallying call for better training, of and engagement with, retrieval teams and more robust data collection to gather, for example, the time that the pancreas is retrieved and the time that the organ is kept on ice before transplant.
The importance of teamwork
Day 2 ends with a wonderful discussion on how exactly to do a whole pancreas transplant and, again, there is much debate between the advantages and disadvantages of bladder drainage versus enteric drainage.
Entire surgical methods are being discussed in depth by a packed room of scientists and clinicians and it reminds me of the importance of multidisciplinary teams. Without the scientists, clinicians could not do their work and without the scientists beavering away at the bench, clinical management and improvements in care would stutter and stumble.
It is a fitting end to a day of biology and medicine right across the spectrum and, as we ourselves stutter and stumble out into the fresh evening air, it is heartening to know that the pancreas and islet transplantation community is so engaged in bringing the collaborative results of research to fruition.
Read the report from Day 1 here
Read more about DRWF-funded islet cell transplantation
Visit the EPITA website