BACKGROUND ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. METHODS Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. FINDINGS With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). INTERPRETATION Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. FUNDING EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).

中文翻译：

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在多中心，非对照试验中，使用自体，扩增的，骨髓源性间充质基质细胞与双相磷酸钙生物材料相关联，治疗胫骨，股骨和肱骨不愈合的可行性和安全性。

背景技术ORTHO-1是一项欧洲多中心的人类临床试验，首次证明在手术植入商业化的双相磷酸钙生物陶瓷颗粒后，手术期间与自体骨髓间充质干细胞（BM-hMSC）结合后可获得的安全性和可行性。制造规范，适用于长骨假关节患者。方法在法国，德国，意大利和西班牙招募了28例股骨，胫骨或肱骨干phy端或干phy端干non端不愈合患者，并对其进行手术治疗，方法是将100或2亿BM-hMSC / mL与5-10 cc生物陶瓷相关联颗粒。对患者进行了为期一年的随访。在所有四个国家中，按照相同的协议扩大了研究用先进治疗药物（ATMP）的使用范围，并获得每个国家主管部门的批准。研究结果以安全性为主要终点，未发现与BM-hMSC相关的严重不良事件。参与的生产中心以可行性作为次要终点，按计划生产了BM-hMSC。将结合到生物陶瓷的ATMP通过外科手术输送给不愈合的关节，发现26/28名接受治疗的患者在一年后接受了放射治疗（4个皮质骨中有3个具有骨桥）。解释安全性和可行性已被临床证明用于生物陶瓷扩大自体BM-hMSC的手术植入。资助EU-FP7-HEALTH-2009，REBORNE项目（GA：241876）。参与的生产中心按计划生产了BM-hMSC。将结合到生物陶瓷的ATMP通过外科手术输送给不愈合的关节，发现26/28名接受治疗的患者在一年后接受了放射治疗（4个皮质骨中有3个具有骨桥）。解释安全性和可行性已被临床证明用于生物陶瓷扩大自体BM-hMSC的手术植入。资助EU-FP7-HEALTH-2009，REBORNE项目（GA：241876）。参与的生产中心按计划生产了BM-hMSC。将结合到生物陶瓷的ATMP通过外科手术输送给不愈合的关节，发现26/28名接受治疗的患者在一年后接受了放射治疗（4个皮质骨中有3个具有骨桥）。解释安全性和可行性已被临床证明用于生物陶瓷扩大自体BM-hMSC的手术植入。资助EU-FP7-HEALTH-2009，REBORNE项目（GA：241876）。