Miami, FL — December 3, 2015 — The Diabetes Research Institute (DRI) will serve as the host institution for the 2015 Annual Investigator meeting of the Human Islet Research Network (HIRN) Consortium of Human Islet Biomimetics (CHIB) on Friday, December 4th, 2015.
HIRN was established in 2014 to help organize and support collaborative research related to the loss of functional beta cell mass in type 1 diabetes (T1D). The project consists of four independent research initiatives including the Consortium on Beta Cell Death and Survival (CBDS), Consortium on Modeling Autoimmune Interactions (CMAI), Consortium on Targeting and Regeneration (CTAR), and Consortium on Human Islet Biomimetics (CHIB), in which the DRI plays a significant role.
The research focus of the CHIB is to combine advances in beta cell biology and stem cell biology with tissue engineering technologies to develop micro-devices that support functional human islets.
DRI Director Camillo Ricordi, M.D., serves as a Principal Investigator from the Diabetes Research Institute/University of Miami on one of the four CHIB funded projects, “Engineering a Human Physiomimetic Islet Microsystem.” Ashutosh Agarwal, Ph.D., Assistant Professor of Biomedical Engineering and Pathology at the University of Miami, and Cherie Stabler, Ph.D., from the University of Florida, also serve as Principal Investigators. Peter Buchwald, Ph.D., Assistant Professor in the Department of Molecular and Cellular Pharmacology and the Director of the Drug Discovery Program, serves as co-investigator.
“At the DRI, this NIH-funded project will allow us to develop the assays and biomarkers needed to identify and characterize health/stress factors that are important to optimize function of insulin-producing cells. This in turn will enable us to define the ideal conditions for survival, differentiation, regeneration and expansion to define ideal conditions for either transplant or research applications,” explains Dr. Ricordi, who is also the Stacy Joy Goodman Professor of Surgery, Distinguished Professor of Medicine, Professor of Biomedical Engineering, Microbiology and Immunology at the University of Miami Miller School. Dr. Ricordi also serves as director of the DRI’s Cell Transplant Center.
Dr. Camillo Ricordi also serves as CHIB representative to the HIRN Islet Advisory Committee (IAC), a select working group which has been created as a means for HIRN Investigators to provide centralized feedback related to the procurement, isolation and analysis of human islets for basic research.
Friday’s meeting will include scientific updates from all four funded groups in the CHIB: A 3D Biomimetic Human Islet to Model Beta Cell Function in Health and Disease ( Maike Sander, MD, University of California at San Diego); A Vascularized 3D Biomimetic for Islet Function and Physiology (Ben Stanger, MD, University of Pennsylvania); Islet on a Chip ( Douglas Melton, PhD, Harvard University) and Engineering a Human Physiomimetic Islet Microsystem ( Cherie Stabler, PhD, University of Florida).
PROJECT ABSTRACTS – CHIB
Engineering a Human Physiomimetic Islet Microsystem
Contact PI: Cherie Stabler, PhD, University of Florida (1UC4DK104208-01)
Ashutosh Agarwal, PhD, Investigator, University of Miami
Camillo Ricordi, MD, Investigator, University of Miami
Peter Buchwald, PhD, co-Investigator, University of Miami
Engineering a Human Physiomimetic Islet Microsystem Type 1 diabetes mellitus, an autoimmune disease resulting in destruction of the insulin- producing pancreatic beta cells, is one of the most common and costly chronic pediatric diseases. A significant impediment to understanding disease pathology and the development of cellular replacement therapies for Type 1 diabetes is the inability to sustain mature human beta cells in culture. In this proposal, we seek to engineer physiomimetic 3D niches within microfluidics devices for maturation, maintenance, and monitoring of human beta cells via the convergence of technologies from stem cell biology, matrix engineering, micro/nano fabrication, and microsensors. The microfluidic devices will connect to universal docks and provide intimate control over the cellular microenvironment by independent and simultaneous modulation of liquid and gas phases, multiparameteric monitoring, and assessment of cellular readouts and samplers for off-line biochemical analyses. With this degree of control, the effect of various niche parameters on human islet maintenance and generation of mature islets from human pancreatic precursors can be clearly delineated. Of particular interest in this application are the contributions of the physiological and extracellular matrix environment on islet health and maturation. Physiological oxygen, a critical parameter in steering pancreatic progenitor differentiation towards endocrine lineage, can be intimately modulated on the microscale via the control afforded by the microfabricated platform. Further, systematic evaluation of the contributions of matrix components on promoting islet health and directing islet differentiation within controlled 3D niches is feasible via tailored presentation of native extracellular matrix components. The ultimate goals of this proposal are twofold: 1) engineer a microfabricated “device and dock” system capable of providing microscale control of soluble and physiological conditions and agile assessment of multiple functional readouts in an enclosed, long-term culture system; and 2) utilize this innovative platform to systematically delineate critical factor capable of supporting both human islet maintenance and maturation of islet-like structures from human pancreatic progenitor cells. The project builds on recent breakthroughs by our team in creating microphysiological systems for other organ systems, engineering perifusion systems, matrix engineering, recreating oxygen controlled microenvironments, and progenitor differentiation. As such, the multidisciplinary consortium assembled herein is well poised to address these grand challenges.