New Grant Supports Study Combining Several Technologies to Advance Cell Replacement Therapy
(June 2011) DRI researchers are combining several novel technologies in an effort to overcome the challenges that have limited cell replacement therapy. Islet transplantation has seen substantial success over the last decade as a treatment for type 1 diabetes. However, despite these promising results, there remain many formidable obstacles to its widespread use. First and foremost is the lack of a plentiful supply of insulin producing cells to treat the expanding number of patients with the disease. Second is the need for powerful immunosuppressive drugs that put patients at risk for devastating complications and have an adverse effect on the function and survival of the transplanted cells. Finally, researchers have been working to determine alternative sites within the body to house transplanted islets that provide a more optimal environment for their long-term survival. Resolving these issues is critical for the development of a clinically-applicable cell transplant therapy for type 1 diabetes.
With the assistance of a $100,000 grant from the Children With Diabetes Foundation, DRI researchers Drs. Chris Fraker and Alice Tomei and their team will embark upon an unprecedented study to overcome these challenges by bridging several different technologies.
>> Conformal coating encapsulation strategy
Encapsulating cells with conformal coating has significant advantages over traditional encapsulation. Previous microencapsulation methods have been met with limited success due to the relatively large amount of space between the islet cell and the wall of the capsule, making it difficult for much-needed oxygen and other nutrients to reach the cell. In addition, the infusion site for encapsulated islets is limited since the procedure cannot be performed safely in well-vascularized sites (those with more blood vessels), like the liver and other areas, because of the large volume of cells created by traditional microencapsulation methods.
The DRI’s Dr. Alice Tomei has recently developed a new encapsulation strategy, known as conformal coating, which significantly reduces both the internal space inside the capsule as well as the the total volume of transplanted cells. The DRI team has already demonstrated that islets encapsulated with conformal coating are capable of reversing diabetes in study models and without conventional immunosuppression. The implications of these findings are enormous, as the reduced size of the capsules allows other sites to be explored.
>> Porcine islets as a plentiful cell supply
Porcine islets have the potential to offer an adequate and reproducible supply of insulin-producing cells. However, since porcine islets come from a different species, they present an additional immunological challenge because they will be quickly rejected by the recipient’s immune system. As a means of addressing this acute rejection, researchers have investigated various encapsulation strategies in order to “mask” the foreign islets from the recipient’s body.
>> Novel oxygen-generating system to sustain cell function and survival
The ideal transplant site is one that is rich with blood vessels since islets require a substantially large amount of oxygen and other nutrients to survive and thrive. In their native environment – the pancreas – islets are surrounded by an abundant vascular network that adequately meets this high demand, allowing the cells to efficiently sense and regulate glucose and insulin secretion. The demand for oxygen is further increased immediately post-transplant when the new islets are required to work extra hard to normalize exceedingly high blood glucose levels.
Understanding this intricate and complex metabolic environment, the DRI team is taking the encapsulation strategy to a new level. In their study, they are taking a synergistic approach to overcoming all of these challenges by transplanting conformally-coated porcine islets into alternative sites of the body and using a novel oxygen generation system that turns on and off in response to changing glucose levels. In addition, since high vascularization is of utmost importance, the team will also provide the transplanted islets with a mechanically supportive matrix that encourages the growth of blood vessels and reduces inflammation at the transplant site.
The central hypothesis of this study is that through the combination of a bio-engineered oxygen delivery system, conformal-coated porcine islets and a bio-active supportive matrix, we can optimize alternative sites for islet transplantation and enhance islet viability and function. The goal is to advance this strategy toward clinical application in patients with type 1 diabetes, which is the primary focus of the Children With Diabetes Foundation.
The Children With Diabetes Foundation was founded by a group of parents of children with diabetes, who want a cure for diabetes. Their executive board consists only of parents of children with diabetes and is 100 percent volunteer run so all money donated goes directly to research. Their team has a vast background in research, science and diabetes. Their mission is to fund human clinical trials leading to cure and prevention of type 1 diabetes. They consider themselves to be the venture capitalists of diabetes research, getting new, clinically relevant, innovative research off the ground.
DRIF's Barbara Singer accepts a $100,000 donation from Ellen Ullman on behalf of the Children With Diabetes Foundation.
Alice Tomei, Ph.D., and Chris Fraker, Ph.D., will lead the DRI team in this effort.