STEM PHARM, INCORPORATED — Department of Health and Human Services SBIR Phase I: 106

Description

Project Summary Abstract Human neural cells manufactured using patient derived induced pluripotent stem cellsiPSCshold great promise for modeling neurodevelopmental disordersdiscovering new precision therapiesand screening for potential risks from environmental toxinsHoweverbiomanufacturing of neural cells and tissues is severely limited by low efficiencypoor reproducibilityand extended timeframesRecent scientific discoveriescoupled with the substantial need for iPSC derived neural cells in pharma applicationsframe a significant commercial opportunityStem Pharm will address this opportunity by commercializing synthetic hydrogel technologies for biomanufacturing of iPSC derived neural cellsSpecificallywe will develop synthetic hydrogel substrates for iPSC derived neural cell expansiondifferentiation and high throughput screening workflowsThe goal of this Phase I project is to develop chemically defined and robust synthetic hydrogels for efficient differentiation of iPSC derived NPCs into cortical neurons and subsequent maturation to post mitoticfunctionally mature neuronsSpecific Aimwill use synthetic hydrogel screening technologies to identify formulations that promote efficient differentiation of NPCs into post mitotic cortical neuronsSpecific Aimwill use synthetic hydrogel screening technologies to identify formulations that promote viabilityretention and accelerated maturation of post mitotic cortical neurons towards functional maturitySpecific Aimwill use a well characterized neurodevelopmental disease line of Rett Syndrome to demonstrate the applicability and advantages of the identified hydrogel formulations for culturing challenging human disease derived cellsThis work is significantas there is a critical need for better tools to optimize yields and reduce variability in the differentiation of iPSCs to defined neural subpopulationssupport their long term cultureand reduce the time needed to reach functional maturitySuccessful completion of the proposed milestones will result in more effective biomanufacturing of neural cells and cell based assays for precision medicineThis work is innovativeas our synthetic hydrogel screening technologies will identify hydrogel formulations for optimal differentiation and maturation of neural populationsThese unique formulations can be discovered using the proprietary hydrogel screening approach developed and used by Stem Pharmbut once identified they can be used broadly across standard pharmaceutical workflowsSubsequent Phase II activities will demonstrate the performance of the unique hydrogel formulations in high throughput screening for toxicity testing and drug discovery Public Health Relevance The use of induced pluripotent stemiPSCtechnologies for disease modeling of neurodevelopmental disorders holds great promise for developing treatment strategiesunderstanding disease etiologies and screening for potential risks from environmental exposuresHoweverthere are current limitations in the differentiation and maturation protocols that need to be improved including growing and differentiating the cells on animal derivedhard substratesWe aim to develop novelsoft synthetic hydrogels that will provide a defined substrate which is more amenable to the culture and differentiation of neural cells