That cell-based therapies will become broadly available to treat diabetes and other diseases without the need for life-long immunosuppression.
To be a global leader in the development and clinical application of cost-effective and widespread of cell-based therapies with a focus on the treatment of diabetes without the need for immunosuppression.
The Institute for Cellular Transplantation at the University of Arizona provides an ideal environment to accomplish this undertaking. Our primary mission will be accomplished by:
- Operating and maintaining a state-of-the-art infrastructure for cell-based therapies at all levels, including technologies, equipment, staff, and support functions
- Manufacturing human islets of the highest standard for clinical transplantation by applying current premium conditions in pancreas procurement, islet cell isolation, islet and organ quality assessment, culture and shipment; and by conducting cutting-edge translational research and development to further enhance islet product manufacturing
- Conducting innovative translational research and development in tissue engineering and bioimaging with a focus on in vitro and in vivo oxygen demand and delivery so as to optimize engraftment and further the successful clinical outcome of cellular therapies in diabetes without the need for immunosuppression
Achievement of these goals requires close interaction and partnership between groups working in engineering, biomaterials, bioimaging, molecular and cellular biology, endocrinology, immunobiology, and transplantation, and infrastructure for the manufacturing, assessment and supply of cell-based products at the highest standard.
The Institute for Cellular Transplantation at the University of Arizona focuses on translational research and development in the area of human islet cell manufacturing and transplantation, addressing the process from organ procurement to delivery of islets, with the goal of optimizing the viable islet yield (highest number of islets at the highest possible quality) per pancreas. Tissue engineering approaches to optimize islet engraftment is another major focus of the institute, which will result in further improvements in the outcome of transplantation and the ability for clinical islet allo-transplantation without the need for life-long immunosuppression. This includes the application of human stem cell derived beta cells and porcine islet xeno-transplantation, which may enable large-scale application of this therapy. We are pursuing five main focus areas for clinical research and development in islet cell-based therapy: Organ Preservation, Islet Manufacturing, Organ and Islet Quality Assessment, Islet Culture and Distribution, and Islet Engraftment.
Major focus areas of the Institute for Cellular Transplantation. These areas are currently in pre-clinical and clinical phases of development. In addition to what is depicted, there is ongoing translational research in new tools and areas of tissue engineering and imaging to further refine and optimize islet cell products and engraftment with the goal of ultimately improving the outcome of transplantation without the need for immunosuppression.
- Organ Preservation
- Islet Manufacturing
- Organ and Islet Quality Assessment
- Islet Culture and Distribution
- Islet Engraftment
In current clinical protocols, islets are transplanted in the liver. It is estimated that more than 50% of the transplanted islets do not engraft and die shortly after infusion. Hypoxia, instant blood mediated inflammatory reaction, and toxicity of immunosuppressive drugs used have been implicated in this substantial islet death, resulting in the need for multiple islet transplants per recipient to achieve insulin independence. A strategy for achieving a highly efficacious, engineered islet graft and site that features localized, sustained delivery of growth and neovascularization-promoting factors, as well as anti-apoptotic and immunosuppressive agents (or cells), along with the transplanted islets is critically needed to improve islet survival and engraftment post-transplantation. In addition, a localized transplantation site has the advantage that it is more amenable to non-invasive imaging techniques for monitoring site and graft performance. Insulin-producing β-cells in islets are extremely fragile and are damaged when deprived of oxygen (hypoxia). Therefore, the ability to monitor a pre-engineered site for oxygen and vascular supply prior to the acceptance of transplanted tissue would greatly enhance the chances of treatment success. The combination of tissue engineering and bioimaging approaches is expected to accelerate the next breakthrough in islet transplantation. Development of biomaterials, probes and methods for non-invasive assessment of pre-engineered localized sites as well as health and oxygenation of transplanted tissue will also benefit other areas of regenerative medicine.
A major focus of the Papas lab current research, which is sponsored by the JDRF Encapsulation Consortium and the NIH/NIDDK, is the successful clinical transplantation of islets or stem-cell derived β-cells to reverse diabetes without the need for immunosuppression using such techniques as described above. The Papas lab utilizes novel methods for in situ oxygen delivery [via a miniaturized wearable and ultimately fully implantable (size of a few pennies), electrochemical oxygen generators] to retrievable vascularization inducing macro-encapsulation immunoisolation devices. Enhanced oxygenation to such immunoisolation devices in vivo can: 1) dramatically reduce the necessary size from that of a 40” flat-screen TV to that of a postage stamp); 2) enhance beta cell functionality (in terms of glucose-stimulated secretion within them); and 3) reduce the dose of cells required to reverse diabetes. If successfully translated to the clinic, the work in this area, conducted in collaboration with Giner Inc. and TheraCyte Inc., has the potential to have a profound impact on reducing overall costs, increasing availability, and improving short-and long-term outcomes of β-cell therapies for the treatment of diabetes while eliminating the need for immunosuppression.
- Suszynski TM, Avgoustiniatos ES, Papas KK. Intraportal islet oxygenation. J Diabetes Sci Technol. 2014;8(3):575-80.
- Papas KK, Avgoustiniatos ES, Suszynski TM. Effect of oxygen supply on the size of implantable islet-containing encapsulation devices. Panminerva Med. 2016;58(1):72-7.
Since joining the University of Arizona in 2011, Dr. Papas has worked on building and integrating his team in the Institute of Cellular Transplantation (ICT) within the Department of Surgery while creating an extensive national and international network of academic and industrial collaborators. These efforts resulted in a strong, externally funded, and highly-visible research program. The total active grant amount for the entire collaborative effort totals more $16 million, with approximately $8 million directly awarded to the U of A with Dr. Papas as the PI.
The majority of these grants are funded by the National Institute of Health (NIH) or the Juvenile Diabetes Research Foundation (JDRF).
For more information on the Institute for Cellular Transplantation, call (520) 626-7167.