Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study.
Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study.
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同种异体形成骨细胞的经皮施用用于治疗延迟骨折的工会的治疗：一项初步研究。
DOI：
10.1186/s13287-021-02432-4
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发表时间：
2021-06-26
影响因子：
7.5
通讯作者：
Sonnet W
中科院分区：
文献类型：
--
作者：
Jayankura M;Schulz AP;Delahaut O;Witvrouw R;Seefried L;Berg BV;Heynen G;Sonnet W
总体而言，5-10%的骨折导致延迟愈合或不愈合，造成严重残疾和巨大的社会经济负担。由于自体骨移植的抢救手术可能会带来额外的挑战，因此已经开发了替代治疗方案来刺激缺陷愈合过程。本研究评估了经皮局部植入异体骨形成细胞治疗长骨骨折延迟愈合的技术可行性、安全性和初步疗效。在这项I/IIA期开放标签试点试验中，22名成人非感染性长骨骨折延迟愈合患者在3 - 7个月后未能巩固，接受了骨髓间充质干细胞（ALLOB; bone Therapeutics）衍生的同种异体骨形成细胞经皮植入骨折部位（50 × 106至100 × 106细胞）。监测患者30个月的不良事件和是否需要抢救手术。采用断层联合评分（TUS）和改良x线联合评分监测骨折愈合情况。使用全球疾病评估（GDE）评分评估健康状况，使用视觉模拟量表评估触诊疼痛。检测反应性抗人白细胞抗原（HLA）抗体的存在。在6个月的随访中，2例患者报告了3例严重的治疗不良事件，其中2例被认为可能与治疗有关。在按方案有效的人群中，21例患者均未在6个月内需要抢救性手术，但2/21（9.5%）患者在治疗后30个月内进行了抢救性手术。治疗6个月后，76.2%的患者TUS改善至少2分，GDE评分平均改善48%，骨折部位触诊疼痛与基线相比平均减少61%。治疗6个月后，含供者特异性hla抗体的血样比例从治疗前的8/22（36.4%）上升至13/22(59.1%)，但未观察到治疗介导的同种异体免疫反应。这项初步研究表明，在长骨骨折延迟愈合的患者中，经皮植入异体骨形成细胞在技术上是可行的，并且耐受性良好。初步疗效证据支持进一步开发这种治疗方法。NCT02020590。注册于2013年12月25日。ALLOB- du1，一项关于同种异体成骨细胞（ALLOB®）植入治疗非感染延迟愈合骨折的有效性和安全性的I/IIa期多中心开放概念验证试验。在线版本包含补充材料，可在10.1186/s13287-021-02432-4获得。
Overall, 5–10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures. In this phase I/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated. During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8/22 (36.4%) before treatment to 13/22 (59.1%) at 6 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed. This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment. NCT02020590. Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures. The online version contains supplementary material available at 10.1186/s13287-021-02432-4.
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DOI：
10.1016/j.bbrc.2012.08.095
发表时间：
2012-10-05
影响因子：
3.1
作者：
Li, Feng;Whyte, Noelle;Niyibizi, Christopher
通讯作者：
Niyibizi, Christopher
影响因子：
4.2
作者：
Hayashi, Ousuke;Katsube, Yoshihiro;Ito, Hiromoto
通讯作者：
Ito, Hiromoto
影响因子：
2.9
作者：
Kakaiya RM;Triulzi DJ;Wright DJ;Steele WR;Kleinman SH;Busch MP;Norris PJ;Hillyer CD;Gottschall JL;Rios JA;Carey P;Glynn SA;National Heart, Lung, and Blood Institute (NHLBI) Retrovirus Epidemiology Donor Study-II
通讯作者：
National Heart, Lung, and Blood Institute (NHLBI) Retrovirus Epidemiology Donor Study-II
DOI：
10.1038/nrrheum.2014.164
发表时间：
2015-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
Hernigou, P;Poignard, A;Rouard, H
通讯作者：
Rouard, H