Use of Stem Cells to Enhance and Extend Continuous Glucose Monitoring in Vivo

Implantable glucose sensor based monitoring of blood glucose levels in diabetic patients has been available for overyearsHoweverdespite improvements to sensor functionalityrecalibration of the sensor device is often a necessity in order to compensate for unreliable sensor performanceThe development of highly accurate and long lived implantable sensors is critical to the development of theartificial pancreasSince it appears that sensor induced tissue reactionsinflammation and wound healinglimits accuracy and lifespan of implanted sensors in vivoit is critical to develop strategies to dramatically enhance the long term biocompatibility of implantable glucose sensorsWe hypothesize that to achieve long term biocompatibility for these sensorswe need to prevent destructive tissue reactions from these sensors andrebuildthe tissue surrounding implanted sensors into asensor friendly tissueTo achieve this goalwe propose to utilize stem cell derivedmicrovesicles exosomesto suppress inflammation and control the structure and function of targeted tissueExosomes are small packages that contain a combination of proteinsDNA and RNAsreferred to asCargowhich are released from activated source cellsExosomes bind to specific target cells andtake controlof the target cell s functionsExosomes targeting and control of target cells is metaphorically similar to the way viruses bind to specific cells and take control of that target cellThe importance of exosomes was underscored by the awarding of theNobel Prize for their discoveryFor the present applicationwe propose to develop exosome matrix based coatings for sensorswhich can be used to enhance sensor biocompatibility and accuracySpecificallywe will focus on mesenchymal stem cellMSCderived exosomes because they are not only anti inflammatorybut also tissue regenerativeBased on the information provided abovewe hypothesize that we can dramatically improve long term sensor accuracy and lifespan in vivoWe plan to develop a novel bioactive sensor coating by incorporating MSC exosomes into our existing basement membrane in order to enhance sensor biocompatibility in vivoThese MSC exosome based sensor coatings are designated as ExoMSC MatrixExo MSC Matrix will be used to coat both transdermal and totally implantable sensorsThese ExoMSC Matrix coated sensors will first be evaluated in our mouse CGM modelEfficacy of this coating will be evaluated through sensor functionas well as histopathology of the implantation sitesIf successful in enhancing sensor function in vivothese MSC exosomes will be analyzed forcargocompositione gDNARNA and proteinsIn the futurethis information can be used to develop designer exosomes by genetically modifying the exosome source cells by the introduction of new genesgene deletions and or regulators of gene expressione gmiRNA gene silencersto create exosomes that will be even more effective in suppressing inflammation and re engineering sensor implantation sites The goal of the present application is to develop a totally new paradigm for biocompatibility coatings for implantable glucose sensors that will utilize antiinflammatory exosome based coatings to prevent inflammation and fibrosisas well as promote tissue re engineering of the sensor implantation sites to allow re utilization of this site for future CGM applications