Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus

Takashi Kamatani, Hiroki Hagizawa, Seido Yarimitsu, Miho Morioka, Saeko Koyamatsu, Michihiko Sugimoto, Joe Kodama, Junko Yamane, Hiroyuki Ishiguro, Shigeyuki Shichino, Kuniya Abe, Wataru Fujibuchi, Hiromichi Fujie, Takashi Kaito, Noriyuki Tsumaki

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


The loss of nucleus pulposus (NP) precedes the intervertebral disk (IVD) degeneration that causes back pain. Here, we demonstrate that the implantation of human iPS cell-derived cartilaginous tissue (hiPS-Cart) restores this loss by replacing lost NP spatially and functionally. NP cells consist of notochordal NP cells and chondrocyte-like NP cells. Single cell RNA sequencing (scRNA-seq) analysis revealed that cells in hiPS-Cart corresponded to chondrocyte-like NP cells but not to notochordal NP cells. The implantation of hiPS-Cart into a nuclectomized space of IVD in nude rats prevented the degeneration of the IVD and preserved its mechanical properties. hiPS-Cart survived and occupied the nuclectomized space for at least six months after implantation, indicating spatial and functional replacement of lost NP by hiPS-Cart. Further scRNA-seq analysis revealed that hiPS-Cart cells changed their profile after implantation, 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, suggesting that chondrocyte-like NP cells are nearly sufficient for NP function. The data collectively indicate that hiPS-Cart is a candidate implant for regenerating NP spatially and functionally and preventing IVD degeneration.

Original languageEnglish
Article number121491
Publication statusPublished - May 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials


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