Professor and CEO CellVoyant Bristol, England, United Kingdom
Abstract: Identifying the regulatory inputs that control and improve cell differentiation to a target cell fate is a fundamental requirement to unravel the mechanisms of organismal development and design strategies to produce cell therapy products efficiently, reproducibly and cost-effectively. Endpoint analytical methods - like immunohistochemistry and omics – are unable to yield continuous insights into cell fate dynamics and transitions, which can only be inferred. By contrast real-time analysis using e.g. genetically-encoded fluorescent reporters can highlight cell fates ‘live’ in a population and yield continuous fate dynamics but is lengthy to implement, cell-type specific and can report only on few cell states simultaneously.
We developed FateView, a technology platform that leverages live-cell imaging, computer vision and AI to enable real-time, non-invasive scalable and predictive monitoring of cell fate dynamics at single-cell level in heterogeneous cell populations. FateView works flexibly across cell types and applications and uses label free imaging for cell predictions, thus requiring no lengthy cell line generation and enabling multiple cell fates to be co-monitored. FateView provides current cell state readouts, predicts future cell states, measures Critical Quality Attributes (CQAs) and differentiation potential and acts as visual digital twin that can evaluate millions of processes in silico and suggest actions to improve outcomes.
Using human Pluripotent Stem Cells (hPSCs), cardiac progenitor cell (CPC) differentiation and retinal pigment epithelial (RPE) cell maturation as exemplars we show that FateView can detect differentiation bias differences across multiple stem cell lines within hours of applying differentiation triggers, significantly faster than conventional endpoint assays. We also show that optimal cell differentiation conditions vary between cell lines, enabling precise line-specific protocol optimisation. Remarkably, all this can be conducted without sacrificing or disaggregating cells or interrupting cell differentiation processes.
By providing a robust flexible and non-invasive platform for monitoring cell fate live, FateView paves the way for novel discoveries and offers a powerful technology to improving cell-based therapies and disease modelling.
