Human neural progenitor cells generated from induced pluripotent stem cells can survive, migrate, and integrate in the rodent spinal cord.

We have previously shown that human neural progenitor cells (NPCs) transplanted into the brain, spinal cord or retina in animal models of disease can survive, migrate, and provide beneficial effects. NPCs can be isolated from different regions of the fetal human brain for expansion in culture and differentiation into neurons and astrocytes. However, human fetal tissue has problematic issues including limited sources and ethical concerns that create a pressing need for alternative sources. Here we describe a new and limitless source of NPCs derived from human induced pluripotent stem cells (iPSCs), which originate from reprogrammed adult somatic cells. iPSCs offer limitless cellular expansion and banking, differentiation into almost any cellular lineage, and an unprecedented opportunity for autologous transplantation. Here, we report a new protocol for the transformation of adherent iPSCs into free-floating NPC spheres (EZ spheres) that are easy to maintain and expand indefinitely using the chopping method. These EZ spheres could be differentiated towards NPC spheres with a spinal cord phenotype. Suspension cultures of NPCs derived from human iPSCs or fetal tissue have similar characteristics, though they were not similar when grown as adherent cells. In addition, iPSC-derived NPCs survived grafting into the spinal cord of athymic nude rats with no signs of overgrowth and with a very similar profile to human fetal-derived NPCs. These results suggest that human iPSC-derived NPCs behave like fetal-derived NPCs and could thus be a novel and valuable alternative for cellular regenerative therapies of neurological diseases.