Safety and efficacy of human juvenile chondrocyte-derived cell sheets for osteochondral defect treatment.
Safety and efficacy of human juvenile chondrocyte-derived cell sheets for osteochondral defect treatment.
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DOI：
10.1038/s41536-021-00173-9
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发表时间：
2021-10-15
影响因子：
7.2
通讯作者：
Okano T
中科院分区：
文献类型：
--
作者：
Kondo M;Kameishi S;Kim K;Metzler NF;Maak TG;Hutchinson DT;Wang AA;Maehara M;Sato M;Grainger DW;Okano T
膝关节软骨损伤后不会自发再生，目前尚未建立金标准的再生治疗算法。这项研究证明了使用热敏培养器皿从常规手术废弃物中生产的无支架人类幼年软骨衍生软骨细胞（JCC）片的临床前安全性和有效性。 JCC 在体外经过 10 代表现出稳定和高生长潜力，支持扩大规模以进行商业化大规模生产的可能性。 JCC 片含有高度存活、密集的细胞，不显示不依赖贴壁的细胞生长，表达间充质表面标记，并且缺乏 MHC II 表达。在裸鼠局灶性骨软骨缺损模型中，通过 JCC 片移植在 4 周时观察到稳定的新软骨形成，在 24 周内没有出现异常组织生长，而未治疗组则没有出现自发软骨修复。再生软骨呈番红-O阳性，含有II型胶原蛋白、聚集蛋白聚糖和人波形蛋白，缺乏I型胶原蛋白，表明形成的透明样新软骨源自移植的JCC片而不是宿主来源的细胞。这项研究证明了 JCC 片材的安全性以及利用可持续组织供应的工程 JCC 片材的稳定透明软骨形成。片材制造和使用的成本效益和缩放问题支持该 JCC 片材策略在临床软骨修复中的可行性。
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.
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影响因子：
2.8
作者：
de Windt TS;Vonk LA;Brittberg M;Saris DB
通讯作者：
Saris DB
影响因子：
9.7
作者：
Arzi B;DuRaine GD;Lee CA;Huey DJ;Borjesson DL;Murphy BG;Hu JCY;Baumgarth N;Athanasiou KA
通讯作者：
Athanasiou KA
DOI：
10.1073/pnas.46.12.1533
发表时间：
1960-01-01
影响因子：
11.1
作者：
HOLTZER, H;ABBOTT, J;HOLTZER, S
通讯作者：
HOLTZER, S
影响因子：
7.2
作者：
Kanzaki, Masato;Takagi, Ryo;Yamato, Masayuki
通讯作者：
Yamato, Masayuki
影响因子：
7
作者：
Katagiri H;Mendes LF;Luyten FP
通讯作者：
Luyten FP