University of Vermont College of Medicine, 226 Health Science Research Facility, Burlington, VT, 05405, USA.
SSI Strategy New York, New York, NY, USA.
Respir Res. 2021 May 8;22(1):142. doi: 10.1186/s12931-021-01734-8.
We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels.
Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels.
In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups.
In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases.
Clinicaltrials.gov NCT00683722.
我们之前报告了一项骨髓来源同种异体间充质干细胞（remestemcel-L）全身给药治疗 COPD 的 1/2 期随机安慰剂对照试验。虽然安全性良好，但未观察到功能疗效。然而，鉴于炎症环境对间充质干细胞作用的影响日益受到重视，我们进行了一项事后分析，并根据循环炎症标志物 C 反应蛋白（CRP）的基线水平进行分层，以确定不同循环 CRP 水平的 COPD 患者接受间充质干细胞给药的效果。
根据基线循环 CRP 水平，将接受 remestemcel-L 或安慰剂四个月输注后的肺功能、运动表现、患者报告的反应和加重频率的时间进程重新评估。
在基线 CRP≥4mg/L 的 COPD 患者中，与接受安慰剂（n=17）的 COPD 患者相比，接受 remestemcel-L（n=12）治疗的患者在 120 天时的一秒用力呼气量、用力肺活量和 6 分钟步行距离均有显著改善，在首次输注后 10 天即可观察到治疗差异。在 CRP 水平≥2 或≥3mg/L 的患者中也检测到了虽然较小但有意义的益处。这些改善在 2 年观察期内持续存在，且具有变异性。在治疗组之间，患者报告的反应或 COPD 加重的次数没有观察到显著的益处。
在炎症环境中，定义为循环 CRP 升高，间充质干细胞给药至少在短期内产生了有意义的肺部和功能改善。这些发现值得进一步研究间充质干细胞治疗 COPD 和其他炎症性肺部疾病的潜在作用。
Clinicaltrials.gov NCT00683722。
