Microfluidic devices have been successfully used in biological assays, especially for assays involving bacteria and cells. While important studies involving bacteria and cells are still in progress in many research laboratories, many devices are now being developed such that tissues, and even organs, can be cultivated on these devices for more realistic biological studies. For nearly a decade, the PI has been culturing endothelial cells in microfluidic devices and investigating the interactions of the endothelium (as a vessel wall tissue) with a flowing stream of blood components such as red blood cells (RBCs) and platelets. In this application, the investigative team wishes to expand upon these tissues to include components of pancreatic tissue (?-cells, the cells responsible for secreting the well-known biological peptide, insulin). One of the major objectives of this application is to measure and understand cell-to-cell and tissue-to-tissue communication between the ?-cells, the bloodstream, and the vessel wall (endothelium). Unfortunately, it has been shown that affecting ?-cells by knockout or knockdown approaches often adversely affects the cell as a whole, thus making it difficult to distinguish key factors in the biological pathways. In this application, the investigative team will develop a novel platform based on 3D-printing of fluidic devices hosting membrane inserts with modified pores that selectively captures molecular messengers traveling through the bloodstream from one tissue to another. We will also develop a new that enables intravenous (IV) injections of drug therapy candidates into a flowing stream of blood or blood components to bridge results into a full in vivo study using animal models of type 1 diabetes (T1D). We hypothesize that the development of this novel platform for studying cell-to-cell and tissue-to-tissue communication can be used as a bridge to in vivo studies involving a possible additional replacement therapy for people with T1D.
Complications associated with type 1 diabetes (T1D) are a major health problem. Here, we describe a novel method of investigating the communication between cells and tissues, without directly manipulating the cells involved, by using modified membranes to selectively capture signaling molecules secreted by the cells. We will use this 3D-printed platform for investigating communication between cells and tissues to investigate the mechanism of a possible new replacement therapy for people with type 1 diabetes involving C-peptide, a molecule that is co-secreted with insulin from the pancreatic ?-cells of healthy individuals.
| Pinger, Cody W; Heller, Andrew A; Spence, Dana M (2017) A Printed Equilibrium Dialysis Device with Integrated Membranes for Improved Binding Affinity Measurements. Anal Chem 89:7302-7306 |
| Pinger, C W; Entwistle, K E; Bell, T M et al. (2017) C-Peptide replacement therapy in type 1 diabetes: are we in the trough of disillusionment? Mol Biosyst 13:1432-1437 |
