Translating Stem Cell Biology Into Drug Discovery

Posted on June 6th, 2018 by admin

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Reprogramming of somatic cells into iPSCs by transient expression of defined transcription factors (OCT4, SOX2, KLF4, C-MYC) is a robust and highly reproducible procedure. However, efficient and controlled multistep differentiation of iPSCs into transient phenotypes and mature functional cells and precise characterization of these cell type identities across developmental states are currently among the greatest challenges in stem cell biology

The CompacT SelecT automated cell culture platform allows standardization and scale-up of iPSCs and their differentiated progeny. Some key features and components of the system are highlighted with arrows. HTS, High-throughput screening.

Summary of the many biomedical opportunities enabled by the iPSC technology (“patient in a dish”). For instance, after generating specific neuronal subtypes representative of various neurotransmitter systems (e.g. glutamatergic, GABAergic, dopaminergic), these cells can be investigated as pure and mixed cultures and subjected to various manipulations (e.g. polypharmacology) for new target identification (ID), predictive toxicology, and other purposes.

Ilyas Singeç and Anton Simeonov

National Institutes of Health (NIH). National Center for Advancing Translational Sciences (NCATS). Division of Pre-Clinical Innovation (DPI)

Abstract

Pluripotent stem cell research has made extraordinary progress over the last decade. The robustness of nuclear reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has created entirely novel opportunities for drug discovery and personalized regenerative medicine. Patient- and disease-specific iPSCs can be expanded indefinitely and differentiated into relevant cell types of different organ systems. As the utilization of iPSCs is becoming a key enabling technology across various scientific disciplines, there are still important challenges that need to be addressed. Here we review the current state and reflect on the issues that the stem cell and translational communities are facing in bringing iPSCs closer to clinical application.