Optimizing Cell Replacement Therapy
Background:
At the Diabetes Research Institute, our scientists are developing new methods of assessing and monitoring the health and quality of islet cells for transplantation. By developing and establishing quality control standards, we can better predict if an islet is healthy enough to respond to blood sugars and normalize glucose levels, and we can monitor that function once cells are transplanted.
Research Focus:
Quality Assessment
Our researchers are studying ways to assess an islet’s ability to survive the transplant process.
- Calcium: Scientists have known for decades that calcium is necessary for insulin secretion. When glucose reaches a beta cell, calcium responds by sending a signal that’s an essential part of the insulin secretion process. Scientists believe that by tracking those calcium signals, we can measure the health and viability of islet cells.
The picture on the right shows beta cells responding to the presence of glucose. Note the color. Islet cells that are bright red show the strongest calcium response, and are the healthiest.
- Laser Scanning Cytometry: One of the more advanced technologies we’re using to view and analyze individual cells is Laser Scanning Cytometry (LSC). This technology helps us to identify, within a group of cells prepared for transplant, how many have died. If the apoptosis (cell death) reaches certain levels, we reject the islets for transplant.
Islet Monitoring
In addition to assessing the health of islets prior to transplantation, we’re also researching ways to monitor the function of insulin-producing cells once transplanted.
At the DRI, we’ve identified certain immune system “markers” that can indicate early islet loss. By monitoring these markers, we can essentially predict islet rejection and intervene with anti-rejection drugs.
We’ve also developed a method for viewing, through sophisticated microscope technology, how transplanted islet cells function when they are inside a living organism.
Living Window
For the first time, our scientists can actually observe insulin-secreting cells inside a living organism. Our scientists have developed a novel method to view functioning transplanted islets in real time. This new technique allows us to study and monitor transplanted tissues with sophisticated microscope technology, as if we were observing the transplants through a window.
Using this state-of-the-art laser technology, we are able to watch the development of the islet cells’ much needed nerve and blood supplies. We can also observe how the immune system launches its attack on the islets cells, something that occurs when the body senses “foreign” tissue as well as with the natural course of type 1 diabetes onset. This real-time monitoring also gives scientists a way to watch the body’s response to new therapeutic strategies that attempt to protect islets from this deadly immune system attack.
Leading to a Cure: How this Research Supports our Mission
In order for cell replacement therapy to become widely accepted as a treatment for diabetes, quality control standards must be established. At the DRI, we’re taking the lead in developing those standards. By transplanting only the healthiest insulin-producing cells, we increase the viability of transplantation as long-term treatment for diabetes.
Human beta cells respond to glucose with an increase in intracellular calcium. Images were obtained with a system that allows simultaneous screening of hundreds of individual islet cells.
DRI scientists can study the physiology of the basic islet components to assess their viability before transplantation.
A clear view of a functioning islet (bright gray) transplanted into the anterior chamber of a mouse eye. Researchers are able to observe the development of blood vessels (red) and can monitor immune responses. In this study, T-lymphocytes (labeled green) travel through blood vessels infiltrating the islet - causing the destruction of the insulin-producing cells. This novel “living window” provides vital information on specific immune system mechanisms and targets and will greatly impact strategies to protect islets.