Microfluidics for Live-Cell Imaging Pancreatic Islets of Langerhans for Human Transplant

Since the introduction of the Edmonton Protocol in 2000, islet transplantation has been emerging as promising therapy for Type I diabetes mellitus (T1DM) and currently is the only therapy that can achieve glycemic control without the need for exogenous insulin. Transplanting islet cells has several advantages over transplanting a whole pancreas in that it involves only a minor surgical procedure with low morbidity and mortality, and at a significantly lower cost. However, an obstacle to realizing this goal is a lack of an islet potency index as required by the U.S. Food and Drug Administration (FDA) biologics licensing, as well as a more complete understanding of the physiological mechanisms governing islet and β-cell physiology. Recently, the University of Illinois at Chicago (UIC) has developed a microfluidic platform that can mimic in vivo islet microenvironments through precise and dynamic control of perifusing culture media and oxygen culture levels; all while measuring functionally relevant factors including intracellular calcium levels, mitochondrial potentials, and insulin secretion. By developing an understanding of the physiology and pathophysiology of islets we can more effectively develop strategies that reduce metabolic stress and promote optimization in order to achieve improved success of islet transplantation and open new clinical avenues. The presentation begins by introducing key issues in the field of pancreatic islet transplantation as a clinical therapy for T1DM. This is followed by brief review various technologies that have been developed to study islet cells. The presentation then describes the design, application, and evolution of UIC’s microfluidic-based multimodal islet perifusion and live-cell imaging system for the study of pancreatic islet and β-cell physiology. The article then concludes presenting initial findings from studies seeking to develop an islet potency test.