Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan.
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Chuo-Ku, Kobe, 650-0017, Japan.
BMC Med. 2023 Oct 5;21(1):386. doi: 10.1186/s12916-023-03088-y.
We previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients.
CD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded.
All fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16-6.85); moreover, no safety concerns were observed.
Our findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion.
UMIN-CTR, UMIN000022814. Registered on 22 June 2016.
我们之前证明，通过成骨作用和血管生成，将 CD34+细胞移植到动物体内可以治愈难治性骨折；我们还在之前的一项 I/II 期临床试验中对 7 名骨折不愈合患者进行了这项细胞治疗的安全性和有效性研究。在此，我们报告了一项 III 期临床试验的结果，该试验使用更大的患者队列来确认之前的研究结果。
通过给予粒细胞集落刺激因子动员 CD34+细胞，使用白细胞分离术采集，然后使用磁性细胞分选分离。15 例胫骨骨不连患者和 10 例股骨骨不连患者接受自体 CD34+细胞移植，移植后随访 52 周。主要结果是与历史对照组患者相比，非愈合患者愈合时间缩短。我们根据 I/II 期研究的结果计算出需要 15 名患者。独立的数据监测委员会进行了影像学评估。记录不良事件和医疗器械故障。
所有骨折均在研究期间愈合。接受 CD34+细胞移植的患者的影像学骨折愈合时间比历史对照组缩短 2.8 倍（危险比：2.81，95%置信区间 1.16-6.85）；此外，未观察到安全性问题。
我们的研究结果强烈表明，自体 CD34+细胞移植是治疗骨折不愈合的一种新的治疗选择。
UMIN-CTR，UMIN000022814。注册于 2016 年 6 月 22 日。
