Multiphoton microscopy gives researchers 'window' into insulin-secreting cells
March 7, 2008, Miami, FL--For the first time ever, diabetes researchers have been able to view how transplanted insulin-secreting cells (islets) function when they are inside a living organism by using confocal multiphoton microscopy. Researchers from the Diabetes Research Institute (DRI) at the University of Miami Miller School Of Medicine and Karolinska Institutet (Stockholm, Sweden) published their findings on line March 7 in Nature Medicine. Although still in the experimental stages of clinical research, islet cell transplantation is currently considered the most promising method for curing type 1 diabetes.
"Up until now we have had no clear way to directly view and monitor how transplanted insulin producing cells function after they are infused into a patient," explains Camillo Ricordi, M.D., scientific director of the Diabetes
Research Institute. "This new technique allows us to study transplanted tissues with sophisticated multiphoton confocal microscopy technology, as if we were observing the transplants through a window in real time. It lets us
follow, biological processes, like the effect of a novel intervention, for example. One of the biggest problems with islet cell transplantation has been having enough of the insulin producing cells survive the transplant process
itself; now we have a window into that living world and this will expedite research considerably."
The DRI scientific team transplanted pancreatic mouse islets into the anterior chamber of a mouse eye, and then viewed the transplant through the cornea, as if it were a living window. After transplantation, the islets actually engrafted on the iris, became vascularized and innervated, retained their cellular make-up, responded to stimulation, and actually reverted diabetes in the animal -- processes that were able to be 'watched' for the first time as they unfolded.
"Using novel laser-scanning microscopy allows you to see deeper into tissue," explains Alejandro Caicedo, Ph.D., research assistant professor of surgery at the Diabetes Research Institute and one of the senior authors of the study. "One of the things we were able to see right away was how the islets established their blood supply, which is a crucial step in the transplantation process because islets need a large blood supply to survive. Although islets make up 1% of the pancreas, they get as much as 40% of the organ's blood supply."
Using this novel technology, DRI researchers were also able to watch how the immune system launches its attack on the islets cells, something that occurs in the natural course of type 1 diabetes onset. This viewing platform
also gives scientists a way to watch the body's response to new therapeutic strategies that attempt to save islets from this deadly immune system attack.
Per-Olof Berggren, Ph.D., professor in experimental endocrinology at Karolinska Institutet adjunct professor of surgery at the Miller School, and the originator of the actual study, explains "that this experimental platform
is invaluable in understanding the molecular mechanisms regulating pancreatic beta cell function and survival subsequent to transplantation. But it is also a versatile tool for studying non-invasively and longitudinally in vivo
endocrine pancreas development, signal-transduction, gene expression and molecular details regarding vascularization and innervation under normal conditions and in diabetes. The experimental platform can also be successfully used for in vivo drug screening in relation to diabetes." (To read the abstract and listen to a podcast by Dr. Berggren, please visit www.diabetesresearch.org)
The unique use of the eye as a research tool to watch islet cell function has now led to a collaboration between the DRI and the Bascom Palmer Eye Institute at the Miller School of Medicine. The two Centers of Excellence plan to further explore the development of the eye as a possible site for islet transplantation.
"It was very exciting to meet with the DRI team when they first showed us the results on the reversal of diabetes following experimental transplantation of insulin producing cells in the eye," said Eduardo Alfonso, M.D., interim chairman, professor, and Edward W.D. Norton Chair in Ophthalmology at Bascom Palmer Eye Institute. "We are looking forward to this collaborative effort to see if this novel approach could one day have a clinical application."