Development of Defined Conditions for Expansion and Dopaminergic Neuron Differentiation of iPSC-derived Neural Progenitor Cells

Human induced pluripotent stem cells (iPSCs) have the capacity to differentiate into all of the somatic cells types and hold great promise for both regenerative medicine and drug discovery. A need for better tools to address neurological disease modeling and neuro-toxicology screening exists. We have developed a scalable process that allows for the generation of large quantities of neural progenitor cells (NPCs) derived from normal and Parkinson’s disease iPSC lines, along with a serum-free defined NPC expansion medium and dopaminergic differentiation medium. To validate the process of NPC derivation, we generated NPCs derived from iPSCs that were reprogrammed with the Sendai virus from the following sources: human foreskin fibroblasts (HFF-1), human CD34⁺ cells, and human fibroblasts from a patient with Parkinson’s disease. Compared to Parkinson’s disease patient-derived NPCs, both normal NPC lines demonstrated greater proliferative capacity. Moreover, our CD34⁺ cell-derived NPCs possessed better tri-lineage differentiation efficiency than that of fibroblast-derived NPCs although all 3 types of NPCs were capable of differentiating into dopaminergic neurons, astrocytes, and oligodendrocytes.