The data collectively indicate that hiPS-Cart is a candidate implant for regenerating NP spatially and functionally and preventing IVD degeneration.Ĭartilage Chondrocytes Induced pluripotent stem cells Nucleus pulposus Regeneration intervertebral disc.Ĭopyright © 2022 The Authors. 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. 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. 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.
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. 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. NP cells consist of notochordal NP cells and chondrocyte-like NP cells. 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. Electronic address: loss of nucleus pulposus (NP) precedes the intervertebral disk (IVD) degeneration that causes back pain.
8 Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Building 17 Second Floor, 2641, Yamasaki, Noda, Chiba, 278-0042, Japan.7 Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.6 Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.5 Technology and Development Team for Mammalian Genome Dynamics, RIKEN BioResource Research Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.4 Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan Department of Tissue Biochemistry, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.3 Department of Mechanical Systems Engineering, Faculty of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan.2 Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan Department of Tissue Biochemistry, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.1 Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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