Under the Microscope with Dora Berman-Weinberg, Ph.D.
As has been reported recently, transplant pateint Wendy Peacock was able to discontinue her insulin therapy after receiving an infusion of islet cells within the omentum as part of the DRI's pilot clinical trial. While Wendy is the first patient to undergo this novel procedure, the DRI has been performing islet transplants in the liver for decades. Many of these patients' donor cells are functioning for 10 years or more, demonstrating that islet transplantation can restore natural insulin production.
Dr. Dora Berman-Weinberg, research associate professor of surgery and member of the DRI’s Cell Transplant Center, is one of our scientists largely involved in the development and testing of new strategies to make the immune system tolerant of transplanted insulin-producing cells. Much of her research is focused in the preclinical phase of testing, in which promising results are then translated to people living with type 1 diabetes. She has also been integrally involved in the development of the biodegradable scaffold, one of the BioHub platforms being tested in the DRI’s new clinical trial.
What is your area of research at the DRI?
I work with Dr. Norma Kenyon and the overall goal of our team is to define strategies that allow us to cure type 1 diabetes through islet cell transplantation. To date, any form of transplant requires the use of life-long drugs that suppress the entire immune system. This is done to prevent immune destruction of the transplanted tissue, but also places the individual at risk for undesired side effects.
We use a pre-clinical model so that promising approaches can be rapidly translated directly into pilot clinical trials. We test the most promising agents that have been identified thus far, including testing extra hepatic sites [outside of the liver] for islet implantation. We also collaborate with our DRI colleagues and other national and international scientists who have any new ideas/approaches to enhance the engraftment and survival of islet or other insulin-producing cells.
You have been working with Dr. Kenyon on co-transplanting MSCs with islets to prolong their survival. What is status of that research?
Dr. Kenyon was awarded a program project from the NIH to pursue work involving the use of mesenchymal stem cells (MSCs) to enhance cellular and solid organ engraftment. The program involves the University of Illinois in Chicago (Dr. Amelia Bartholomew, kidney transplant model), the U of Illinois at Urbana-Champaign (Dr. Kenton McHenry, data mining and analysis) and the Scripps Research Institute, La Jolla (Dr. Daniel Salomon, genomics). The goal of the islet transplant project is to define the impact of the MSC source (from an islet donor, islet recipient or unrelated third party) on islet transplant survival, to verify that MSCs can reverse rejection episodes and to utilize the knowledge gained to develop a clinical protocol. The work has gone well, and we have begun discussions with Drs. Camillo Ricordi and Rodolfo Alejandro to outline what a clinical protocol should look like.
You were also very involved in the development of the biodegradable scaffold. Can you tell us how that idea developed?
I had attended the Annual Meeting of the American Transplant Congress to present a poster on the preclinical transplantation of islets within a synthetic scaffold placed in an omental pouch. While there, I learned of another interesting approach using a blood plasma clot. I thought the concept of using blood from the recipient to create a biological scaffold held a good deal of promise and wanted to consider testing a similar approach in our models.
Serendipitously, while we were already performing some tests in our lab, I happened to accompany my husband to have a dental implant and learned that dentists have been using patients’ own blood to create a gel that helps with bone grafting in these procedures. This corroborated the idea that biological scaffolds could also be beneficial for islet cell implants.
We developed our own unique strategy and then tested the approach in a preclinical model. The results were very encouraging and supported the feasibility and clinical translational potential of the approach. As it often happens in science, this was indeed a team effort, validating the notion that “it takes a village.”
What are the latest results of your research using the omentum?
The current site for clinical islet transplantation is the liver, however the liver has several disadvantages that result in loss of functional islet mass. The omentum meets the requirements for a successful alternative site for islet transplant. Our data show that islets transplanted within a plasma-thrombin resorbable gel onto the omentum engraft and survive. A clinical pilot trial is underway at the DRI to translate our findings to the clinic and explore the safety and efficacy of this approach in patients with T1D under standard immunosuppression.