Induced pluripotent stem cells from discovery to translation.

Abstract

Two decades after the introduction of induced pluripotent stem cell (iPSC) technology, the field has evolved from a seminal biological discovery into a transformative clinical platform. This maturation reflects a convergence of nonintegrating cellular reprogramming, efficient differentiation protocols, high-fidelity tissue engineering and precise genome editing-which together have established a platform-level framework for recapitulating and probing human disease biology in human cell-based systems. While these milestones have enabled the first wave of iPSC-based therapeutic clinical trials and recent early approvals, the transition to standardized, widely deployable therapies remains constrained by inherent biological variability, manufacturing complexities and the need for long-term safety surveillance. This Review evaluates the technological and translational trajectories that have defined the iPSC era and analyzes the operational barriers to therapeutic development. Looking forward, we discuss how integrating automation and artificial intelligence could redefine iPSC workflows as scalable systems. We present a roadmap for the next 20 years, envisioning a paradigm shift in which iPSC-derived interventions transition from bespoke experimental models toward standardized, engineered biological medicines.