Abstract
The transplantation of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) has beneficial effects on spinal cord injury (SCI). However, while there are many subtypes of NPCs with different regional identities, the subtype of iPSC-derived NPCs that is most appropriate for cell therapy for SCI has not been identified. Here, we generated forebrain- and spinal cord-type NPCs from human iPSCs and grafted them onto the injured spinal cord in mice. These two types of NPCs retained their regional identities after transplantation and exhibited different graft-host interconnection properties. NPCs with spinal cord regional identity but not those with forebrain identity resulted in functional improvement in SCI mice, especially in those with mild-to-moderate lesions. This study highlights the importance of the regional identity of human iPSC-derived NPCs used in cell therapy for SCI.
Highlights
Spinal cord injury (SCI) is a devastating and incurable disease, and basic treatment has not yet been developed
Generation of human induced pluripotent stem cells (iPSCs)-derived neural progenitor cells (NPCs) with specific regional identities To generate region-specific NPCs from human iPSCs, we first regulated Wnt and retinoic acid (RA) signaling during neural induction as previously described [20] (Fig. 1a)
Wnt-inhibited (FB-type) cells showed high expression of the forebrain marker FOXG1 and EMX1, and the spinal cord marker HOXB4 and HOXC4 were upregulated in Wnt/RA-activated (SC-type) cells, whereas the NPC marker NESTIN was not affected by these signaling modulators (Fig. 1b, c, S1A)
Summary
Spinal cord injury (SCI) is a devastating and incurable disease, and basic treatment has not yet been developed. Many studies suggested that the functional improvement of SCI model animals was achieved by the transplantation of fetal cells with multiple origins, such as the spinal cord [9, 10], the forebrain [11, 12], and the peripheral tissues [13]. It has been recently demonstrated that the original identity of transplanted fetal NPCs is important for tissue regeneration and functional restoration [14, 15]. In these studies, fetal spinal cord NPCs resulted in better effects than NPCs with other original identities. The underlying mechanisms remain to be understood, these studies suggest
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