Administration of Adult Human Bone Marrow-Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger's Disease: Phase II Study Report Suggests Clinical Efficacy.
Administration of Adult Human Bone Marrow-Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger's Disease: Phase II Study Report Suggests Clinical Efficacy.
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DOI：
10.5966/sctm.2016-0237
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发表时间：
2017-03
影响因子：
6
通讯作者：
Majumdar AS
中科院分区：
文献类型：
--
作者：
Gupta PK;Krishna M;Chullikana A;Desai S;Murugesan R;Dutta S;Sarkar U;Raju R;Dhar A;Parakh R;Jeyaseelan L;Viswanathan P;Vellotare PK;Seetharam RN;Thej C;Rengasamy M;Balasubramanian S;Majumdar AS
由Buerger病引起的严重肢体缺血(CLI)是一种发病率很高的未得到满足的主要医疗需求。这项II期前瞻性、非随机、开放标签、多中心、剂量范围的研究是为了评估肌注的有效性和安全性。由于Buerger病，在CLI中注射成人骨髓来源的、培养的、混合的同种异体间充质干细胞(BMMSC)。患者被分成三组：1和200万细胞/公斤体重组(各36例)和标准护理(SOC)组(18例)。骨髓间充质干细胞在小腿肌肉和溃疡周围局部注射40-60次。大多数患者是年轻人(年龄范围38-42岁)和既往吸烟者，所有患者都至少有一次溃疡。在接受200万细胞/公斤体重的组中，主要终点-减少休息疼痛(每月0.3个单位[SE，0.13])和溃疡愈合(每月减少11%的面积[SE，0.05])-都明显好于SOC组。与SOC组相比，接受200万个细胞/公斤组的次要终点也有显著改善，如踝臂压力指数(每月增加0.03[SE，0.01]个单位)和总步行距离(1.03[SE，0.02倍/月])。报告的不良事件与骨髓间充质干细胞有远程相关或无关。总而言之，I.M.骨髓间充质干细胞的剂量为200万个/公斤，显示出临床益处，可能是治疗Buerger病所致CLI患者的最佳方案。然而，还需要进一步的随机对照试验来确定最合适的剂量。干细胞转化医学2017；6：689-699
Critical limb ischemia (CLI) due to Buerger’s disease is a major unmet medical need with a high incidence of morbidity. This phase II, prospective, nonrandomized, open‐label, multicentric, dose‐ranging study was conducted to assess the efficacy and safety of i.m. injection of adult human bone marrow‐derived, cultured, pooled, allogeneic mesenchymal stromal cells (BMMSC) in CLI due to Buerger’s disease. Patients were allocated to three groups: 1 and 2 million cells/kg body weight (36 patients each) and standard of care (SOC) (18 patients). BMMSCs were administered as 40–60 injections in the calf muscle and locally, around the ulcer. Most patients were young (age range, 38–42 years) and ex‐smokers, and all patients had at least one ulcer. Both the primary endpoints—reduction in rest pain (0.3 units per month [SE, 0.13]) and healing of ulcers (11% decrease in size per month [SE, 0.05])—were significantly better in the group receiving 2 million cells/kg body weight than in the SOC arm. Improvement in secondary endpoints, such as ankle brachial pressure index (0.03 [SE, 0.01] unit increase per month) and total walking distance (1.03 [SE, 0.02] times higher per month), were also significant in the group receiving 2 million cells/kg as compared with the SOC arm. Adverse events reported were remotely related or unrelated to BMMSCs. In conclusion, i.m. administration of BMMSC at a dose of 2 million cells/kg showed clinical benefit and may be the best regimen in patients with CLI due to Buerger’s disease. However, further randomized controlled trials are required to confirm the most appropriate dose. Stem Cells Translational Medicine 2017;6:689–699