Primorigen Biosciences (R) Abstract Primorigen Biosciences will use SBIR funds to develop a novel commercial assay that measures the toxicity of compounds on human induced pluripotent stem cells (hiPSCs) differentiating into hematopoietic progenitor cells (HPCs) and on HPCs differentiated from hiPSCs. The assay will rely on Primorigen's highly efficient, patent-pending MesoTotal" medium for differentiating hiPSCs into HPCs. Phase I studies will optimize HPC differentiation and analysis for high-throughput screening formats, determine toxic impact that compounds have on hiPSCs differentiating into HPCs, and screen for compounds that exhibit toxicity towards hematopoietic progenitor cells derived from hiPS cells. In Phase II, we will enhance commercial applications by a) adapting the system to 384-well HTS formats, b) increasing genetic diversity by including additional hiPSC lines, c) testing a larger library and mixtures indicative of typical environmental exposure, and d) completing secondary screenings to establish dosing efficacy and mechanism of actions. In Phase III, the assay system will be evaluated for potential pharmaceutical development applications. The commercial application is a robust scalable human assay system for screening to assess compound toxicity against hiPS cells differentiating into HPCs.
Current methods for toxicology screening rely on animal models or transformed human cell lines, neither of which can recapitulate fully the developmental processes and mature cell phenotypes of human tissues. Human induced pluripotent stem cell (hiPSC) -derived hematopoietic progenitor cells (HPCs) offer a unique cell source for examining the effects of toxicants upon differentiation processes and upon the mature hematopoietic progenitor cell. Primorigen Biosciences will develop a high throughput hematopoietic progenitor cell screening method that will enable screening of compound libraries for toxic effects.