Autologous mesenchymal stromal cells embedded in tricalcium phosphate for posterolateral spinal fusion: results of a prospective phase I/II clinical trial with long-term follow-up
Autologous mesenchymal stromal cells embedded in tricalcium phosphate for posterolateral spinal fusion: results of a prospective phase I/II clinical trial with long-term follow-up
复制标题
DOI：
10.1186/s13287-019-1166-4
复制
发表时间：
2019-02-22
影响因子：
7.5
通讯作者：
Sanchez-Guijo, Fermin
中科院分区：
文献类型：
--
作者：
Blanco, Juan F.;Villaron, Eva M.;Sanchez-Guijo, Fermin
腰椎后外侧融合加自体骨移植被认为是腰椎退行性间盘病(DDD)手术治疗的金标准。目的分析自体骨髓间充质干细胞植入磷酸三钙替代植骨的安全性、可行性和潜在临床疗效。研究设计I/II期单臂前瞻性临床试验。自体骨髓来源的MSC在我们的良好制造规范(GMP)设备中进行扩增，并在脊柱手术中植入磷酸三钙载体中。对患者的监测包括术后12个月，4次随访(第1、3、6、12个月后)，临床和放射学评估，包括视觉模拟评分(VAS)、奥斯维斯特里残疾指数(ODI)、简明健康调查(SF-36)、通过简单的X线片观察椎体融合分级，以及评估可能的并发症或不良反应。结果中位年龄44岁(30~58岁)，男女之比为(6/5)L4~L5，L5~S1DDD分别为5例和6例。所有病例的自体骨髓间充质干细胞均有扩增。未发现与细胞植入相关的不良反应。在疗效方面，术后VAS和ODI评分均有改善。放射学上，80%的患者在随访结束时完成了腰椎融合。结论自体骨髓间充质干细胞用于单节段退行性腰椎间盘疾病患者的脊柱融合术是可行的、安全的、潜在的有效的。EudraCT：2010-018335-17；代码标识：NCT01513694(Clinicaltrials.gov)。
BackgroundPosterolateral spinal fusion with autologous bone graft is considered the gold standard for lumbar degenerative disc disease (DDD) when surgical treatment is indicated. The potential role of mesenchymal stromal cells (MSCs) to replace the bone graft in this setting has not been fully addressed.ObjectiveTo analyze the safety, feasibility and potential clinical efficacy of the implantation of autologous MSCs embedded with tricalcium phosphate as a therapeutic alternative to bone graft in patients with DDD during posterolateral spine fusion.Study designPhase I/II single-arm prospective clinical trial.MethodsEleven patients with monosegmental DDD at L4-L5 or L5-S1 level were included. Autologous bone marrow-derived MSC were expanded in our Good Manufacturing Practice (GMP) Facility and implanted during spinal surgery embedded in a tricalcium phosphate carrier. Monitoring of patients included a postoperative period of 12months with four visits (after the 1st, 3rd, 6th, and 12thmonth), with clinical and radiological assessment that included the visual analog scale (VAS), the Oswestry disability index (ODI), the Short-Form Health Survey (SF-36), the vertebral fusion grade observed through a simple Rx, and the evaluation of possible complications or adverse reactions. In addition, all patients were further followed up to 5years for outcome.ResultsMedian age of patients included was 44years (range 30-58years), and male/female ratio was (6/5) L4-L5 and L5-S1 DDD was present five and six patients, respectively. Autologous MSCs were expanded in all cases. There were no adverse effects related to cell implantation. Regarding efficacy, both VAS and ODI scores improved after surgery. Radiologically, 80% of patients achieved lumbar fusion at the end of the follow-up. No adverse effects related to the procedure were recorded.ConclusionsThe use of autologous MSCs for spine fusion in patients with monosegmental degenerative disc disease is feasible, safe, and potentially effective.Trial registrationno. EudraCT: 2010-018335-17; code Identifier: NCT01513694 (clinicaltrials.gov).