"Engineering a Bioartificial Pancreas"

Cherie Stabler, PhD
Associate Professor, Biomedical Engineering
Diabetes Research Institute

Abstract
A closed loop, glucose sensing, and insulin responsive system could dramatically improve treatment options for insulin dependent diabetics. Clinical islet transplantation, the intrahepatic loading of allogeneic islets, shows the potential to provide this intimate control, by transplanting the very cells with this inherent glucose sensing/insulin secreting capacity. The success of clinical islet transplantation is hindered by the location of the implant site, which is prone to mechanical stresses, inflammatory responses, and exposure to high drug and toxin loads, as well as the strong inflammatory and immunological response to the transplant in spite of systemic immunosuppression. To address these challenges, we are focused on three primary strategies: the development of scaffolds to house islets at alternative transplant sites; the fabrication of encapsulation protocols for the immuno-camouflage of the transplant; and the production of bioactive biomaterials for the local delivery of oxygen and immunomodulatory drugs and/or cells. Three-dimensional scaffolds can serve to create a more favorable islet engraftment site, by ensuring optimal distribution of the transplanted cells, creating a desirable niche for the islets, and promoting vascularization. Encapsulation can substantially decrease the need for systemic immunosuppression of the recipient, by preventing host recognition of surface antigens. Finally, localization of supportive agents to the site of the transplant can serve to enhance efficacy, while minimizing the side effects observed with systemic delivery. Success in these strategies should increase the efficacy of islet transplantation for the treatment of Type 1 Diabetes, whereby the long-term survival and engraftment of the transplanted islets are significantly improved.

Biography
Cherie Stabler, PhD, is a tenured Associate Professor in the Departments of Biomedical Engineering, Surgery, and Biochemistry & Molecular Biology at the University of Miami.  Stabler also serves as the Director of the Tissue Engineering Program at the Diabetes Research Institute at the University of Miami. She received her Ph.D. in Biomedical Engineering from The Georgia Institute of Technology & Emory University. Her research centers on the engineering of cell-based tissues for the treatment of Type 1 diabetes, specifically the development of novel biomaterials for: cellular encapsulation; three-dimensional scaffolds; and in situ oxygen and drug release. Through the fabrication of novel biomaterials capable of actively interfacing with the host, she seeks to modulate the graft environment to favor the survival and optimal function of the implanted cells. She has published in a broad range of journals, from the Proceedings of the National Academy of Science, to Biomacromolecules, to Cell Transplantation. She is a recipient of the 2008 NIH NIDDK Type 1 Diabetes Pathfinder DP2 Award. Her research is supported by the National Institutes of Health, the Juvenile Diabetes Research Foundation, the Helmsley Trust, and the Diabetes Research Institute Foundation.