Skip to 0 minutes and 20 seconds So Toby you’re involved in islet cell transplants. Tell me why is that so important. Well, it’s a cell therapy Gordon. So it’s an example of a new technology where we’re able to actually correct the problem that somebody with type 1 diabetes has, by giving back the thing that they’re missing, which is the cells. Now we can do this by doing a whole pancreas transplant. But of course, for most people with type 1 diabetes anyway, the rest of the pancreas, the exocrine portion works perfectly normally. Transplantation, as we currently practice it, relies on deceased organ donation. That is, somebody dying and generously donating their organs.
Skip to 0 minutes and 59 seconds And if that person isn’t the right age, with the right body build, and they’re not diabetic themselves, the pancreas can then be shipped to either Melbourne or Sydney where there are two expert isolation facilities. In those isolation facilities the pancreas is broken down into its constituent parts, and the insulin secreting cells, or the islets, are separated out from there. Those islets can then be purified on a quite expensive machine, and then potentially available for transplantation back. So that’s the first issue. And the problem is that the isolation techniques themselves are quite inefficient, so that we do lose quite a number of cells just purely in isolation.
Skip to 1 minute and 42 seconds The second issue then is once you’ve got the cells, is how to give them back. At the moment, how we give them back is into the liver. And that’s the world standard. That’s what we do. But the problem with the liver is, it’s basically a terrible site to put cells. It’s a terrible site because the oxygen level in the liver is very low. And islets are exquisitely sensitive to oxygen. So they like to be well vascularized. The oxygen tension in the liver is about 50 [INAUDIBLE] 50 Venous blood is quite low. The second issue is there is not a well formed network of capillaries in the liver to receive the islet cells.
Skip to 2 minutes and 17 seconds So not only are they in blood that’s got low oxygen, but they’re starved because new blood vessels take two weeks to grow in. During that time the islet cells themselves can die. There’s a profound immunological inflammatory reaction that happens in the portal circulation too, which is called the instant blood mediated inflammatory response. Far too hard to say, so we call it IBMIR. Now IBMIR destroys, we think, in combination with the hypoxia and the immune system in the liver up to 75% of the cells. So you don’t need to be a mathematician to realize that it’s incredibly inefficient. So firstly, we have difficulties getting the cells.
Skip to 2 minutes and 53 seconds And secondly the site that we put into, you potentially lose 2/3 of them within the first 24 hours. So clearly there’s a pressing need in this field to come up with alternative ways to deliver the cells, to stop those fundamental processes from happening.
Skip to 3 minutes and 14 seconds The big advantage of the three dimensional printing is the ability to precisely locate the cell that you want in an environment that you wish to make it. And secondly, the ability to modify that environment in the inks that you used to actually print it. So for example, we spent a long time looking at the factors that make islets happy and not happy. And we know that many of those factors such as glycosaminoglycans, various chondroitin sulfates, heparin sulfate, various growth factors like parasite growth factor, like insulin-like growth factor 2, for example– all of these factors if applied in the right amount, to the right cell, at the right time can protect them from whatever stress we’re applying to them externally.
Skip to 3 minutes and 55 seconds So the fact that you can generate bio-inks and that you’ve got expertise in modifying those with these molecules immediately makes the printing inherently attractive, because it means that we could potentially supplement things that the cells might be missing in this difficult transition from isolation back into a person. The second aspect of it that I think is inherently appealing is the idea that we can co-locate other cell types with the islet cells. So we know, for example, that vascular cells, or in particular endothelial progenitor cells are very useful for islets, because they secrete a range of factors that potentially make the islets function better. One of those is a factor called VGEF, vascular individual growth factor.
Skip to 4 minutes and 37 seconds So to some extent, we don’t actually need to supplement the ink with VGEF if we can put the cell that’ll make that factor right next to it. So having a bio printer and the prospect of having one before the end of the year for example, really gets the guys in the lab going because this is the cutting edge. This is what we all want to do. We all want to do things that impact people. And if we can do something that impacts on type 1 diabetes here in Australia we’ll have a true global reach and global impact.
Skip to 5 minutes and 9 seconds So for this application we need to be able to build a structure that will retain the islet cells in place, and also allow us to discretely position other cells or growth factors within the scaffold structure itself. Typical extrusion printing isn’t going to be sufficient enough. We need to be able to incorporate another printing process that will allow us to have that fine control, positioning small volumes of material. In this case, we’re going to use micro-valve ink jet dropping. As you can see graphically here, we have a robust scaffold structure that’s been produced by coaxial extrusion printing. Encaged within in that scaffold structure are the islet cells themselves.
Skip to 5 minutes and 46 seconds And then discreetly positioned throughout that structure at individual points are growth factors and other cell types. So in order to achieve this we need to develop a new technology does allows us to take a device like the biopen and use that and incorporate it with other technologies together to give us an integrated printing approach that will allow us to produce micro-scale and micro-scale features within a scaffold structure.
Skip to 6 minutes and 17 seconds The program with three axis stage allows us to position the extrusion material anywhere in three dimensional space, allows us to have fine control over that extrusion material, but also allows us the capability to integrate another deposition device, such as a micro-valve dropper or an inkjet head that would then be able to discretely position our secondary material within the scaffold structure.
Islet cell transplants
A new corrective therapy
Type 1 diabetes
New technology and advances in 3D bioprinting could address issues concerning cell transplantation. Similarly, the technology can be harnessed to enable islet cells to be successfully introduced into the liver.
“… it’s an example of a new technology where we’re able to actually correct the problem that somebody with type 1 diabetes has, by giving back the thing that they’re missing, which is the cells.” (Professor Patrick Toby Coates, Director of Kidney and Pancreatic Islet Transplantation, Royal Adelaide Hospital)
© University of Wollongong, 2020