Clinical translation of pluripotent stem cell-based therapies: successes and challenges

Abstract

The translational stem cell research field has progressed immensely in the past decade. Development and refinement of differentiation protocols now allows the generation of a range of cell types, such as pancreatic β-cells and dopaminergic neurons, from human pluripotent stem cells (hPSCs) in an efficient and good manufacturing practice-compliant fashion. This has led to the initiation of several clinical trials using hPSC-derived cells to replace lost or dysfunctional cells, demonstrating evidence of both safety and efficacy. Here, we highlight successes from some of the hPSC-based trials reporting early signs of efficacy and discuss common challenges in clinical translation of cell therapies.

Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson’s disease

“…Parkinson’s disease (PD) is an incurable neuro-degenerative disorder, the motor symptoms of which are caused by a relatively selective loss of dopamine (DA) neurons in the substantia nigra. Engraftment of VM DA progenitors to the putamen to replace the lost endogenous cells is a promising restorative therapeutic strategy to ensure continuous DA release at physiological levels (Barker and Björklund, 2023), and several approaches are currently in clinical trial (Christiansen and Kirkeby, 2024). The differentiation protocols used to generate VM DA progenitors from human pluripotent stem cells (hPSCs) have been improved by adjusting early patterning with growth factors (Doi et al, 2020; Kim et al, 2021; Nishimura et al, 2023; Nolbrant et al, 2017).…”