Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities
Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities
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DOI：
10.1016/j.jcyt.2020.02.007
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发表时间：
2020-06-01
期刊：
影响因子：
4.5
通讯作者：
O'Brien, Timothy
中科院分区：
文献类型：
--
作者：
Mohamed, Sara Azhari;Howard, Linda;O'Brien, Timothy
背景：严重肢体缺血（CLI）是周围血管疾病最严重的表现。血运重建是首选治疗方法，但由于疾病的弥漫性解剖分布或合并症，25%-40% 的患者无法实现血运重建。无选项 CLI 代表未满足的医疗需求。间充质基质细胞（MSC）可以通过其血管生成和组织营养特性提供挽救治疗。本文报道了一项 lb 期临床研究，检验自体骨髓 MSC 肌内移植治疗无选择 CLI 患者的安全性和可行性。方法：12 例患者入组临床试验，9 例进行骨髓抽吸和培养扩增 MSC。结果：在产生的细胞中检测到高核型异常率（>30%） 批次，导致临床用药放行失败。 4 名患者接受了研究药物 (IMP) 治疗，其中 3 名患者接受低剂量 20 x 10(6) MSCs 治疗，1 名患者接受中剂量 40 x 10(6) MSCs 治疗。没有发生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。结论：该试验的结果得出结论，使用 MSC 治疗严重肢体缺血的自体细胞治疗方法因核型异常率高而受到限制。 (C) 2020 年国际细胞和基因治疗学会。由爱思唯尔公司出版
Background: 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 lb clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI.Methods: Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs.Results: 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 x 10(6) MSCs and one with a mid-dose of 40 x 10(6) MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy.Conclusions: 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. (C) 2020 International Society for Cell and Gene Therapy. Published by Elsevier Inc.