Interview with Cherie Stabler, Ph.D.
The DRI is pursuing many cell-based treatments to replace insulin function in people with diabetes, including islet transplantation, xenotransplantation (other species), transdifferentiation and stem cell research. Success in these research areas will largely depend upon the ability to protect the insulin-producing cells from the body’s strong immunological and inflammatory responses that can inhibit long-term function and health.
Cherie Stabler, Ph.D., director of the Tissue Engineering Laboratory at the Diabetes Research Institute and assistant professor of biomedical engineering at the University of Miami School of Engineering, is investigating methods to combine engineering materials and biochemical factors with cells and other tissue. Her research focuses on designing devices for implantation, developing materials to combat inflammatory and immunological responses to the islets during transplantation, and investigating methods to non-invasively monitor the implants.
By combining engineering materials and biochemical factors with cells and other tissue, Dr. Stabler and her team are designing and developing innovative approaches to encase, or coat, the transplanted insulin-producing cells with a protective, biocompatible substance that could shield the cells from the body’s immune system and improve their viability.
How can tissue engineering impact the success of islet transplants?
I see the area of tissue engineering as an approach that can complement other research strategies. For example, I believe that designing a device to adequately support the nutrient needs of the islets and developing materials to dampen the recognition of the islets by the immune system can be combined with a targeted, moderate immuno-suppressive regimen to improve the effectiveness of a transplant.
What islet-focused projects are you working on now?
We are developing nano-encapsulation strategies that will help minimize the large inflammatory response seen during transplantation and camouflage the implant from the immune system. We are also developing techniques to help improve engraftment of the islet by increasing nutrient delivery or creating an anti-inflammatory environment. We are using mathematical models and engineering tools to design macro-encapsulation devices to house islets in a site alternative to the liver. We also are engineering biomaterials that will assist in mechanically protecting the islets once transplanted.
Would you explain the differences between macro-, micro- and nano-encapsulation as they relate to islet transplants?
Macro-encapsulation is the confinement of all of the transplanted islets within a single implantable device. The advantage of this method is that you have a single device that can be easily retrieved, refilled and monitored. The disadvantage is that when you have all of the islets compacted within one space, you develop problems with delivering enough nutrients to all of the cells.
Micro-encapsulation is the encapsulation of a small number of islets, usually no more than three, within a single micro-sized capsule. Multiple capsules are transplanted at the same time. The advantages of this technique include improved nutrient delivery and response times; however, the disadvantages are that there is still a large barrier between the islet and its surroundings; this technique creates an increased overall volume of the transplant; and it becomes more difficult to remove the capsules once implanted.
Nano-encapsulation is a more recent technique that is being used to hide the islets from the host’s immune system. Nano-scale layers of biomaterials are applied and conform to the outer surface of the islet, thereby masking the surface proteins that typically trigger the inflammatory and immune responses of the host. The major advantage of this method is that it only imparts a very small film on the outer surface of the islet, which minimizes or eliminates any problems with nutrient delivery. This method could be used in conjunction with the macro-encapsulation design, allowing for better monitoring and retrievability with improved immune protection.
Could you explain noninvasive monitoring and how this would benefit patients?
In our research, the goal of noninvasive monitoring is to develop a means to assess the function of a cell-based implant without having to use invasive tools. An example of this would be to use MRI (magnetic resonance imaging) to obtain images of the implanted islets and directly assess their metabolic activity. This is an area of research that is still in its infancy, but it could prove to be very useful to monitor the status of an implant in vivo. If we can develop a tool to measure islet function accurately, we may be able to predict the failure of an implant before the physiological effects (such as the loss of glycemic control) have manifested.
How important is collaboration in your research?
In my previous experience, I worked in a highly collaborative environment with scientists from vastly different backgrounds. I learned that many cutting edge projects emerge when interacting with scientists from different disciplines. Similarly, the highly interdisciplinary approach of the DRI is a founding principle of its Tissue Engineering Program. We are in collaboration with several researchers at the DRI, in addition to several external researchers in the fields of biomaterials, stem cells and noninvasive monitoring. I believe that only through strong collaborations with people from different backgrounds can truly innovative developments be made.
Dr. Stabler received her Ph.D. as a joint degree from Georgia Tech and Emory University. She did her postdoctoral fellowship in the Department of Surgery at Emory.