Klearchos Papas, Ph.D. Photo by Scott Streble
Discoveries in Diabetes
Imaging and engineering offer intriguing new ideas for improving islet cell transplants
By Mary Hoff
When the idea of transplanting insulin-producing islet cells first emerged many years ago, hope ran high that a cure for type 1 diabetes could be just on the horizon. Reality, however, has yet to catch up with the dream.
Islets are not easy to keep alive through pancreas procurement, preservation and islet isolation, purification, and infusion into the liver, where the cells ideally begin producing insulin for their new host. Most transplants appear successful at first, but after two years more than half of recipients are back to needing other sources of insulin.
Klearchos Papas, Ph.D., director of islet processing research and development with the University’s Schulze Diabetes Institute, aims to change that with the use of nuclear magnetic resonance (NMR), which can provide information about the quality of islets and also pinpoint the location of islets within the body. The University is a world leader in these technologies, allowing researchers to see the body in ways they have never seen it before.
Papas and colleague Bruce Hammer, Ph.D., of the Department of Radiology developed an NMR compatible pancreas preservation container making it possible to noninvasively and nondestructively check the health of the pancreas before islet isolation. Islet isolation alone can cost more than $20,000, so there is value in being able to distinguish between viable and nonviable cells early in the process. If cells are compromised, the process is halted, saving time, money, and dashed hopes.
Currently, Papas is exploring a collaboration with researchers at the University’s Center for Magnetic Resonance Research (CMRR) to monitor and improve the fate of islets after transplantation. The idea is to use NMR to see where the islets engraft and at what point islets lose viability under various protocols so procedures can be improved. “We don’t have a way to do that post-transplant except to look at blood sugar,” Papas says.
That’s where he’s hoping to tap the expertise of CMRR associate director Michael Garwood, Ph.D. An internationally renowned imaging scientist, Garwood is experienced in developing novel techniques for applying magnetic resonance to solving research problems. And he is already involved in diabetes research of another sort. For more than a decade, Garwood and Elizabeth Seaquist, M.D., director of the Center for Diabetes Research, together with several other CMRR scientists, have collaborated on efforts to use magnetic resonance to look at glucose and glycogen in the brain. Seaquist believes these substances could hold the key to understanding and overcoming hypoglycemia unawareness, a sometimes-fatal condition in which persons with diabetes fail to recognize when their blood sugar levels plummet too low.
Garwood’s colleague Greg Metzger, Ph.D., and Papas are exploring ways to apply NMR to noninvasively assess islet location and islet health simultaneously. That capability would be invaluable for pinpointing when things start to go awry after transplant. “That’s where CMRR has succeeded—in developing new imaging techniques used to measure not just anatomy, but physiology, function, and a lot more,” Garwood says.
Papas is also enthusiastic about involving Garwood and Metzger in a project with colleagues in the Department of Chemical Engineering and Materials Science to use biomaterials to protect islets against stress during transplantation and onslaught by the immune system afterward.
Magnetic resonance technology could prove invaluable in testing such materials as they are being perfected. It could also help improve islet survival by making sure blood vessels surrounding the implantation site are developed enough to support the transplant.
Papas’s overarching goal is to be able to keep islets healthy before, during, and after transplant. “That’s the vision, but there’s lot of work to be done,” he says.