National University of Ireland Galway, Ireland. Regenerative Medicine Institute.
Health Research Board, Clinical Research Facility Galway, Ireland.
Cytotherapy. 2020 Jun;22(6):313-321. doi: 10.1016/j.jcyt.2020.02.007. Epub 2020 Apr 6.
Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI.
Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs.
A high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 10 MSCs and one with a mid-dose of 40 × 10 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy.
The results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.
严重肢体缺血（CLI）是外周血管疾病最严重的表现。血运重建是首选疗法，但由于疾病的弥漫性解剖分布或合并症，仍有 25%-40%的患者无法实现血运重建。无选择CLI 代表了未满足的医疗需求。间充质基质细胞（MSCs）可能通过其血管生成和组织营养特性提供挽救性治疗。本文报告了一项 1b 期临床研究，该研究检查了自体骨髓 MSCs 肌肉内移植治疗无选择 CLI 患者的安全性和可行性。
12 名患者入组临床试验，其中 9 名患者进行骨髓抽吸和 MSC 培养扩增。
生产的细胞批次中检测到高比例的染色体异常（>30%），导致无法放行用于临床给药。4 名患者接受了研究药物（IMP）治疗，3 名患者接受了低剂量 20×10 MSCs 治疗，1 名患者接受了中剂量 40×10 MSCs 治疗。没有与试验干预相关的严重不良事件，包括骨髓抽吸、IMP 注射或治疗。
该试验结果表明，MSCs 治疗严重肢体缺血的自体细胞治疗方法受到染色体异常率高的限制。
