This article presents a refined approach to Parkinson's disease cell therapy. The researchers developed SphereDiff, a robust three-dimensional (3D) culture method for generating high-purity midbrain dopaminergic progenitors (mDAPs) from human pluripotent stem cells (hPSCs). By applying a novel cross-transplantation single-cell split barcoding (TX-SISBAR) technique, they traced the clonal lineage fates of donor cells after transplantation, revealing that off-target glutamatergic neurons primarily derived from diencephalic progenitors. This lineage-guided refinement using stepwise WNT activation successfully eliminated off-target cells in the donor population, resulting in grafts that yield nearly pure mDA neurons, fully restoring dopamine levels and motor function in Parkinson’s disease mouse models.
References:
- Zhang X, Wu Z, He H, et al. 3D-generation of high-purity midbrain dopaminergic progenitors and lineage-guided refinement of grafts supports Parkinson’s disease cell therapy[J]. Cell Stem Cell, 2025.
