{
  "abstract": "Introduction Autologous and allogeneic chondrocyte cell sheet transplantation has shown safety and potential efficacy for cartilage defects associated with knee osteoarthritis. Although polydactyly-derived chondrocyte (PDC) cell sheets have been used clinically for allogeneic transplantation, a scalable and reliable alternative cell source is needed. This study aimed to establish a proof-of-concept protocol for generating chondrocyte cell sheets from clinical-grade human induced pluripotent stem cells (iPS cells). Methods Cartilaginous tissue was generated from human iPS cells, and isolated chondrocytes were used to fabricate iPS cell-derived chondrocyte sheets. In Phase 1, sheets were produced in high-serum medium under normoxic, hypoxic, or hypoxic/high-seeding-density conditions and compared with PDC sheets using a three-dimensional in vitro model and xenogeneic orthotopic transplantation in an immunodeficient rat model. In Phase 2, sheets were produced in low-serum medium under hypoxic/high-seeding-density conditions and evaluated for cartilage-related gene expression, secreted factors, cell surface marker expression, and in vivo cartilage repair. Results In Phase 1, hypoxic/high-seeding-density culture enhanced in vitro chondrogenic properties. However, after transplantation, iPS cell-derived chondrocyte sheets formed fibrotic repair tissue, whereas PDC sheets generated hyaline-like cartilage. In Phase 2, low-serum culture increased expression of cartilage-related genes, including collagen type II alpha 1 (COL2A1) and SRY-box transcription factor 9 (SOX9), enhanced secretion of transforming growth factor beta 1 and melanoma inhibitory activity, and upregulated CD9, CD26, CD56, CD201, CD227, and GD2. Low-serum iPS cell-derived chondrocyte sheets regenerated hyaline cartilage at 4 weeks, and the repair tissue was maintained at 12 weeks without bone formation. Conclusions A robust fabrication protocol enabled human iPS cell-derived chondrocyte sheets to regenerate hyaline-like cartilage in vivo. These findings support their potential as a scalable cell source for clinical cartilage repair.",
  "abstract_shown": true,
  "affiliations": [
    "Tokai University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "T. Takahashi"
    },
    {
      "name": "R. Uchiyama"
    },
    {
      "name": "E. Toyoda"
    },
    {
      "name": "M. Maehara"
    },
    {
      "name": "Y. Takahashi"
    },
    {
      "name": "S. Wasai"
    },
    {
      "name": "H. Oomura"
    },
    {
      "name": "M. Ogawa"
    },
    {
      "name": "A. Yamashita"
    },
    {
      "name": "M. Watanabe"
    },
    {
      "name": "N. Tsumaki"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Sato"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bkp3rpntbqtdw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754531",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754531v1.full",
  "id": "bkp3rpntbqtdw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754531v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioengineering"
    ],
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7214680402",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754531v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bkp3rpntbqtdw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:50Z",
      "native_id": "10.64898/2026.09.25.754531",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754531v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Enhancing the hyaline cartilage regenerative potential of induced pluripotent stem cell-derived chondrocyte cell sheets",
  "title_text": "Enhancing the hyaline cartilage regenerative potential of induced pluripotent stem cell-derived chondrocyte cell sheets",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:50Z",
  "url": "https://research.draconitic.com/paper/bkp3rpntbqtdw",
  "venue": "bioRxiv",
  "versions": []
}