The Stabler Diabetes Tissue Engineering Laboratory is distinguished by its integration of engineering, biomaterials, and transplantation in a highly translational manner. Research topics within the laboratory are diverse in the generation of functional materials, but highly focused on translational research in the field of diabetes. Our laboratory philosophy is one that seeks to build strong interdisciplinary collaborations to integrate biological cues and signals with rationally designed biomaterials. Through this integration, novel platforms can be developed that not only serve to provide the basic framework to the tissue, but to also dynamically interact and instruct the surrounding host cells and environment on how to respond to the implant. In such a manner, superior implants may be developed that provide elegant and localized control of the implant microenvironment.
The primary focus of the research within the Diabetes Tissue Engineering laboratory is to develop engineering platforms for improving cellular therapies, with a focus on treating Type 1 Diabetes. Tissue Engineering involves the use of living cells and biomaterials to develop biological substitutes for implantation into the body with the purpose of replacing, repairing, or regenerating diseased tissues. Within the area of tissue engineering and diabetes, we are focused on the development of novel biomaterials for improving cell-based transplantation, specifically 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, we seek to modulate the graft environment to favor the survival and optimal function of the implanted cells.
Type 1 diabetes mellitus is a serious autoimmune disease resulting in destruction of the insulin-producing pancreatic beta cells. A desire to provide a treatment option that duplicates the normal physiological response to glucose has stimulated research in the development of both an artificial and bioartificial pancreas. It is our belief that a bioartificial pancreas, or cell-based system, based on the transplantation of insulin secreting cells, would provide a superior treatment for diabetes mellitus, by harnessing the cell’s inherent capacity to provide responsive glucose sensing and physiological insulin secreting system. At the forefront of biological replacement therapy is clinical islet transplantation (CIT), which currently involves the infusion of allogeneic islets into the liver. While CIT is very promising, it has become evident that inflammatory and immunological host responses, as well as the suboptimal nature of the liver site, lead to significant islet dysfunction and destruction, thereby decreasing the duration of graft efficacy. The early loss of transplanted islets has been partially attributed to the hepatic engraftment site, where as much as 60% of the islets may be lost. Additional islet loss occurs due to delays in islet revascularization, mechanical stress to the islets, toxicity of systemic immunosuppression and the persistence of allograft rejection and recurrent autoimmunity, in spite of these immunosuppression regimens. Therefore, there is a strong need to investigate alternative transplant sites and supporting scaffolds that could provide a means to bypass these significant inflammatory and mechanical stresses, as well as provide an optimal site for islet engraftment. In addition, the development of methods to dampen or eliminate the need for systemic immunosuppression could make a significant impact on the field of islet transplantation.
As Type 1 Diabetes is a multi-faceted disease, it requires highly collaborative, multi-disciplinary teams pushing the technology forward to the clinic. Our laboratory thrives on strong collaborative connections between researchers from a wide variety of backgrounds, such as immunologists, cell biologists, chemists, transplant surgeons, molecular biologists, and engineers. As engineers in this space, we can provide guidance on improving cellular therapies to make them more effective and safer. With the focus on cure-based research, the goals of our laboratory are to continually pursue strategies that can be quickly translated to the clinical arena.
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Dr. Stabler’s research is funded by federal and private agencies. Specifically:
The NIH Human Islet Research Network (HIRN) via a UC4 grant within the Consortium on Human Islet Biomimetics (CHIB) with project “Engineering a Human Physiomimetic Islet Microsystem“
The NIH NIDDK via a R01 grant “Engineering Ultrathin Immunomodulatory Coatings for Islet Encapsulation“,
The JDRF and the Leona M. and Harry S. Helmsley Charitable Trust by projects:
“Engineered Bioactive Hydrogel Macrodevices for Islet Transplantation: Engineering an Optimal Site for Islet Transplantation”
“Development of an Extrahepatic Site for Beta Cell Replacement without Continuous, Systemic Immunosuppression”
“New islet encapsulation method for ideal mass transport and immunoprotection”