Human iPS cell-derived cartilage spatially and functionally replaces nucleus pulposus

Single cell RNA sequencing (scRNA-seq) analysis identified notochordal nucleus pulposus (NP) cells and chondrocyte-like NP cells in NP. Cells in human induced pluripotent stem cell-derived cartilage (hiPS-Cart) corresponded to chondrocyte-like NP cells but not to notochordal NP cells. hiPS-Cart cells changed their profile after implantation into intervertebral disks of nude rats, differentiating into two lineages that are metabolically distinct from each other. However, post-implanted hiPS-Cart cells corresponded to chondrocyte-like NP cells only and did not develop into notochordal NP cells. We performed a single cell (sc)RNA-seq transcriptome analysis of nucleus pulposus (NP) and articular cartilage (AC) of cynomolgus monkey and compared the results with a scRNA-seq analysis of human induced pluripotent stem cell-derived cartilage (hiPS-Cart). Then hiPS-Cart was implanted into nuclectomized spaces of intervertebral disks of coccygeal vertebra in nude rats. Six weeks later, the implants were harvested and subjected to scRNA-seq analysis.