Dataset Information

Safety and efficacy of human juvenile chondrocyte-derived cell sheets for osteochondral defect treatment.

ABSTRACT: Knee cartilage does not regenerate spontaneously after injury, and a gold standard regenerative treatment algorithm has not been established. This study demonstrates preclinical safety and efficacy of scaffold-free, human juvenile cartilage-derived-chondrocyte (JCC) sheets produced from routine surgical discards using thermo-responsive cultureware. JCCs exhibit stable and high growth potential in vitro over passage 10, supporting possibilities for scale-up to mass production for commercialization. JCC sheets contain highly viable, densely packed cells, show no anchorage-independent cell growth, express mesenchymal surface markers, and lack MHC II expression. In nude rat focal osteochondral defect models, stable neocartilage formation was observed at 4 weeks by JCC sheet transplantation without abnormal tissue growth over 24 weeks in contrast to the nontreatment group showing no spontaneous cartilage repair. Regenerated cartilage was safranin-O positive, contained type II collagen, aggrecan, and human vimentin, and lacked type I collagen, indicating that the hyaline-like neocartilage formed originates from transplanted JCC sheets rather than host-derived cells. This study demonstrates the safety of JCC sheets and stable hyaline cartilage formation with engineered JCC sheets utilizing a sustainable tissue supply. Cost-benefit and scaling issues for sheet fabrication and use support feasibility of this JCC sheet strategy in clinical cartilage repair.

SUBMITTER: Kondo M

PROVIDER: S-EPMC8520001 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Safety and efficacy of human juvenile chondrocyte-derived cell sheets for osteochondral defect treatment.

Kondo Makoto M Kameishi Sumako S Kim Kyungsook K Metzler Nicolas F NF Maak Travis G TG Hutchinson Douglas T DT Wang Angela A AA Maehara Miki M Sato Masato M Grainger David W DW Okano Teruo T

NPJ Regenerative medicine 20211015 1

Knee cartilage does not regenerate spontaneously after injury, and a gold standard regenerative treatment algorithm has not been established. This study demonstrates preclinical safety and efficacy of scaffold-free, human juvenile cartilage-derived-chondrocyte (JCC) sheets produced from routine surgical discards using thermo-responsive cultureware. JCCs exhibit stable and high growth potential in vitro over passage 10, supporting possibilities for scale-up to mass production for commercializatio ...[more]

PMID: 34654830

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Project description:Repairing cartilage tissue is a serious global challenge. Herein, we focus on wood skeletal structures that are highly porous for cell penetration yet have load-bearing strength, and aim to synthesize wood-derived hydrogels with the ability to regenerate cartilage tissues. The hydrogels were synthesized by wood delignification and the subsequent intercalation of citric acid (CA), which is involved in tricarboxylic acid cycles and essential for energy production, and N-acetylglucosamine (NAG), which is a cartilage glycosaminoglycan, among cellulose microfibrils. CA and NAG intercalation increased the amorphous region of the cellulose microfibrils and endowed them with flexibility while maintaining the skeletal structure of the wood. Consequently, the CA-NAG-treated wood hydrogels became twistable and bendable, and the acquired stiffness, compressive strength, water content, and cushioning characteristics were similar to those of the cartilage. In rabbit femur cartilage defects, CA-NAG-treated wood hydrogels induced the differentiation of surrounding cells into chondrocytes. Consequently, the CA-NAG-treated wood hydrogels repaired cartilage defects, whereas the collagen scaffolds, delignified wood materials, and CA-treated wood hydrogels did not. The CA-NAG-treated wood hydrogels exhibit superior structural and mechanical characteristics over conventional cellulose-fiber-containing scaffolds. Furthermore, the CA-NAG-treated wood hydrogels can effectively repair cartilage on their own, whereas conventional natural and synthetic polymeric materials need to be combined with cells and growth factors to achieve a sufficient therapeutic effect. Therefore, the CA-NAG-treated wood hydrogels successfully address the limitations of current therapies that either fail to repair articular cartilage or sacrifice healthy cartilage. To our knowledge, this is the pioneer study on the utilization of thinned wood for tissue engineering, which will contribute to solving both global health and environmental problems and to creating a sustainable society.

Dataset Information

Safety and efficacy of human juvenile chondrocyte-derived cell sheets for osteochondral defect treatment.

Publications

Safety and efficacy of human juvenile chondrocyte-derived cell sheets for osteochondral defect treatment.

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