Donor Age Impairs Vasculogenic Potential of hiPSC-Derived Endothelial Progenitors via Elevated Mitochondrial Reactive Oxygen Species

Larsen and colleagues compared endothelial progenitors derived from hiPSCs made from three neonatal and three mature donors. Cells from mature donors formed less connected and less lumenized vascular structures in vitro. The authors linked donor age with methylation and gene-expression differences, higher mitochondrial reactive oxygen species and lower mitochondrial membrane potential. An antioxidant improved network formation in the mature lines tested. The result is relevant to the quality and reproducibility of cell products because donor age may influence the performance of a differentiated iPSC product even after reprogramming. It does not show that an iPSC therapy works in people, and it does not establish that antioxidant treatment would improve a clinical graft. The study has a very small donor panel, relies on laboratory assays rather than transplantation, and is a preprint. It adds a manufacturing and biological-age consideration to the iPSC evidence base. It does not justify an evidence-grade upgrade for stem-cell interventions or any longevity ingredient.

Our findings highlight donor age as a critical determinant of hiPSC-EC vasculogenic function and identify mitochondrial ROS as a targetable mechanism.