Instrumented human stem cells to see more during high throughput screening in drugInstrumented human stem cells to see more during high throughput screening in drug discovery and regenerative medicine

Projektbeschreibung

Verbesserung des Hochdurchsatz-Wirkstoffscreenings mit Stammzellen

Induzierte pluripotente Stammzellen sind eine Art von Stammzellen, die durch Reprogrammierung erwachsener Zellen, in der Regel aus Haut- oder Blutproben, in einen pluripotenten Zustand erzeugt werden. Pluripotente Stammzellen haben die Fähigkeit, sich in viele verschiedene Zelltypen im Körper zu differenzieren. Das vom Europäischen Forschungsrat finanzierte Projekt hiPSCmore zielt darauf ab, die Hochdurchsatz-Bildgebung für die Pharmaforschung und die regenerative Medizin unter Verwendung menschlicher induzierter pluripotenter Stammzellen zu verbessern. Die Idee ist, fluoreszierende Sensoren in menschliche induzierte pluripotente Stammzellen einzubauen, um so die Kosten für das Screening zu senken und die Effizienz zu erhöhen. Bei der Untersuchung sollen die technologische Machbarkeit dieses Ansatzes bewertet und die Marktdynamik analysiert werden, um einen größeren Anteil des Marktes für Hochdurchsatz-Wirkstoffscreening zu erobern.

Ziel

"In hiPSCmore (read hiP-See-More), my team and I will engineer fluorescent sensors in the DNA of human induced pluripotent stem cells (hiPSC) so we can “See More” during high-throughput imaging screenings (imHTS) for drug discovery and regenerative medicine.

Since hiPSCs can differentiate in most cell types in the human body, they are the ideal cell source for more predictively screening therapies. Yet, hiPSCs are expensive to maintain and require external reagents to visualize pathophysiological changes, which adds to the screening cost and complexity. In fact, the major hurdle in adopting hiPSCs for imHTS has been the price increase from <0.10 $/data point to 2+ $/data point.

In the context of our ERC Stg, we genetically encoded fluorescent sensors for cell structure, function, and cell cycle progression directly into hiPSCs for in-vitro modeling of heart development. With those sensors, we can visualize pathophysiological changes through reagents provided by the cells themselves. Thus, the more experiments we conduct, the cheaper they become. We believe this is the strategy to bring hiPSCs into imHTS, where testing millions of compounds vanishes an experiment's marginal cost. Like software.

To explore this opportunity, we envision three main objectives.
1. Technology feasibility. We will scale up the production of our SeeMore hiPSCs and validate their cost-effectiveness in drug screening and regenerative medicine applications.
2. Business feasibility. We will analyze market dynamics and customer preferences in the drug screening and regenerative markets to define the most efficient go-to-market strategy.
3. Executive management. We will work with stakeholders in our advisory board to delineate IPR, business strategy, and future fundraising opportunities for a SeeMore spin-off company.

Through these activities, the SeeMore spin-off will incorporate the right mix of tech development and business savvy in its own DNA, so it can ""seize more"" of the HTS market."