オカノ テルオ   OKANO Teruo
  岡野 光夫
   所属   医学研究科 医学研究科 (医学部医学科をご参照ください)
   職種   評議員
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Differentiated and Untreated Juvenile Chondrocyte Sheets Regenerate Cartilage Similarly In Vivo.
掲載誌名 正式名:Tissue engineering. Part A
略  称:Tissue Eng Part A
ISSNコード:1937335X/19373341
掲載区分国外
巻・号・頁 pp.Epub ahead of print
国際共著 国際共著
著者・共著者 Metzler Nicolás F†, Kondo Makoto*, Matsukura Keisuke, Ford Adam J, Grainger David W, Okano Teruo
発行年月 2024/11
概要 Osteoarthritis, a degenerative disease of articular cartilage and the leading cause of disability, is preceded by acute cartilage injury in a significant proportion of cases. Current auto- and allograft interventions are limited by supply and variability in therapeutic efficacy, prompting interest in tissue engineering solutions. Cell sheet tissue engineering, a scaffold-free regenerative technique, has shown promise in preclinical and clinical trials across various cell types and diseases. Polydactyly-derived juvenile cartilage-derived chondrocyte (JCC) sheets from juvenile patients are a potent cell source for developing allogeneic therapies. JCC sheets have proven safe and effective in animal models and as an add-on therapy in a recent clinical cartilage repair study. However, JCC ex vivo expansion leads to de-differentiation, contributing to long healing times. This study hypothesized that in vitro differentiation of JCC sheets into hyaline-like cartilage constructs could accelerate cartilage regeneration without compromising implant integration. To this end, sheet integration, maturation, and healing of conventionally prepared vs. differentiated JCC sheets were compared in an established nude rat focal chondral defect model. Differentiated JCC sheets exhibit mature cartilage phenotypes prior to transplant. Both conventional and differentiated JCC sheets are reliably transplanted without additional fixation. Histological evaluation reveals that both transplant groups produced equivalent neocartilage regeneration, filling defects with mature hyaline cartilage at 2- and 4-weeks post-transplant. Notably, differentiated JCC sheets respond to in vivo signals, undergoing matrix remodeling and integration with adjacent and subchondral tissue. Given equivalent healing outcomes, the future utility of in vitro JCC sheet predifferentiation from other JCC donors with different healing capacities should be balanced against their increased culture costs over conventional shee
DOI 10.1089/ten.tea.2024.0208
PMID 39556329