Miami, FL (February, 2009) — Scientists from the Diabetes Research Institute will report on their latest research findings in key cell therapies aimed at reversing diabetes at two prestigious international conferences: the American Transplant Congress in Boston, MA, (May 30-June 3, 2009) and the 69th Scientific Sessions of the Annual American Diabetes Association in New Orleans, LA (June 5-9, 2009).
Joining hundreds of the top professionals in the fields of transplantation, diabetes research and the delivery of diabetes care and services, participants from the DRI will include Rodolfo Alejandro, M.D., Alejandro Caicedo, Ph.D., Ronald Goldberg, M.D., Norma S. Kenyon, Ph.D., Alberto Pugliese, M.D. and Jay Skyler, M.D., among others.
Key Signals Profiled in Type 1 Diabetes
Dr. Alberto Pugliese, head of the DRI’s Immunogenetics Program, will report on his new findings involving the presence of a select group of key “master regulators” in people with type 1 diabetes. Together with DRI colleague, Dr. Ricardo Pastori, director of the Molecular Biology Laboratory, the team identified a population of these tiny genes that create signals called microRNAs (miRNA).
These signals then regulate key biological events, such as cell proliferation (growth) and the transformation of stem cells into functional adult cells. They also play a critical role in the development and maintenance of diseases.
A preliminary study showed that patients with type 1 diabetes had a dramatic increase of a specific miRNA compared to those without diabetes. While limited to five families, the findings suggest that miRNAs may be a powerful marker to predict the development of type 1 diabetes.
In related work, another group of miRNAs has shown to play a central role in islet development. It is believed that they also play a major role in expanding the number of islets and increasing insulin production during the high metabolic demands of pregnancy. These observations have sparked great interest in the development of strategies to introduce miRNA’s into stem cells and other tissue as a way to expand the number of insulin-producing cells to treat those with diabetes.
New Sites for Cellular Transplants
Dr. Norma S. Kenyon, co-director of the DRI’s Executive Research Council, will present her work testing alternative transplant sites for islets. Traditionally, the liver has been used for these cell transplants but mounting evidence suggests that new approaches may offer a safer and less toxic environment for these transplanted cells.
Dr. Kenyon will describe studies involving the creation of a living “pouch” as part of the recipient’s omentum, a highly vascularized “curtain” that covers the abdomen. Her presentation will be part of the the ADA’s symposium titled: Islet Transplantation – Barriers and Prospects.
Dr. Kenyon will also report on the DRI’s progress using targeted radioisotope therapy as a way to promote immune tolerance to transplanted tissue. The treatment is used to shrink or reduce the recipient’s bone marrow to provide “space” for donor bone marrow to take up residence.
The co-existence of the donor and recipient bone marrow, known as chimerism, has been shown to re-educate the recipient to accept transplanted tissue from the same source as the bone marrow donor. The challenge has been to achieve chimerism using safe and effective methods for the recipient. Dr. Kenyon will report that the use of this compound increases the occurrence of chimerism in preclinical models.
Using Bone Marrow-Derived Cells to Enhance Islet Engraftment
Dr. Kenyon will present results of a preclinical study using a population of bone marrow-derived mesechymal stem cells (MSCs) co-transplanted with islets. The goal was to assess the ability of the mesechymal stem cells to enhance islet engraftment and reverse rejection episodes. Dr. Kenyon and her team observed significant enhancement of islet engraftment and function compared to recipients that did not receive the mesechymal stem cells. Multiple infusions of MSCs were also able to reverse rejection as well as prolong islet function.
In other studies, these cells have been instrumental in repairing damaged tissue. They have also shown the ability to stimulate the growth of blood vessels, as well as significantly reduce inflammation, suppress the immune response to transplanted islet cells and may also support the production of new insulin-producing cells.
The results of this recent study in a clinically relevant model suggest that mesechymal stem cells may offer a new approach to improve islet engraftment and decrease the numbers of islets currently needed to achieve insulin independence. It may also pave the way for safe and effective anti-rejection therapy.
Survival and Function of Transplanted Islets into a Biohybrid Device
DRI researchers will present data showing that long-term islet cell allograft survival can be achieved using a prevascularized, subcutaneous (under the skin) device. The DRI’s development of a biohybrid device allows blood vessels to grow in and around the mesh “cage” before implanting the islets into this device. This provides the oxygen-rich environment essential for islets survival and proper function.
Researchers noted that the choice of immune intervention appears to be critically important to allow the cells to engraft within the device and achieve full function after the islet implantation. These results lay the groundwork for further development of the device for future clinical application.