Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus. (May 2022)

• Record Type: Journal Article
• Authors: Kamatani, Takashi; Hagizawa, Hiroki; Yarimitsu, Seido; Morioka, Miho; Koyamatsu, Saeko; Sugimoto, Michihiko; Kodama, Joe; Yamane, Junko; Ishiguro, Hiroyuki; Shichino, Shigeyuki; Abe, Kuniya; Fujibuchi, Wataru; Fujie, Hiromichi; Kaito, Takashi; Tsumaki, Noriyuki
• Is Part Of: Biomaterials. Volume 284(2022)
• Publication Date: 2022-05
• Subjects: Induced pluripotent stem cells -- Regeneration -- Nucleus pulposus -- Cartilage -- Chondrocytes -- intervertebral disc; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121491
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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.