JDRF – UVA Microfluidic-Based Beta-Cell Functional Analysis Facility
The Microfluidic-based beta-cell functional analysis facility is located in the Department of Surgery at the University of Virginia (UVA) and is supported by the Juvenile Diabetes Research Foundation International (JDRF). This functional analysis facility will provide an analysis and characterization service for emerging islet cell derivatives including hESCs/hiPSCs, microencapsulated islets/hESCs/hiPSCs, as well as screening of potential pharmaceutical agents for diabetes treatment. This service will be available to the JDRF community as a whole and diabetes researchers who may not have such technology or access.
The overall purpose is to assist the field of diabetes research in moving forward with therapeutic strategies for beta-cell replacement and beta-cell regeneration to cure Type I diabetes. Additionally, we are also willing to service those who are working on islet or beta-cell related research.
Islet cell derivatives will be analyzed to answer the following basic questions:
(1.) Compared to human islets, do the biologics have similar physiological response profiles in the presence of glucose or other secretagogues?
(2.) Physiologically, what are the functional similarities and/or dissimilarities of the biologics to human islets?
(3.) Does the biologics have normal or altered insulin stimulator-secretion coupling factors and what, if any, is the impact of pathophysiological changes on insulin secretion?
(4.) How does microencapsulation and hypoxia impact the function and survival of microencapsulated islet cells?
In 2009, we designed a three-layer microfluidic perifusion device specifically for pancreatic islets of Langerhans
(Fig.1A). This initial design has evolved into a family of microfluidic devices that can be applied to the study of islet physiology and pathophysiology (Fig.1B-E). In the current system, islet fixation is not required.
Specific chemical gradients can be established and well maintained in the perifusion chamber (Fig.2A). The microfluidic perifusion system
measures not only insulin secretion kinetics but also insulin stimulator-secretion coupling factors by integrating with multiparametric optical imaging technology, including measurement of calcium influx, mitochondrial potentials, NAD(P)H, ROS, glucose uptake (individually or combined two or three simultaneous fluorescence imaging) (Fig2B).
In addition to insulin measurements, additional islet hormones can be measured with tested spatiotemporal resolution including; proinsulin, C-peptide, and glucagon (Fig.2C). Furthermore, various islet types, single beta-cells, and encapsulated islet cells can be analyzed (Fig.2D).
José Oberholzer, M.D.
Yong Wang, M.D.
Phone: 847-224-6099Complete a Service Form