Chacon Alberty Lourdes, Perin Emerson C, Willerson James T, Gahremanpour Amir, Bolli Roberto, Yang Phillip C, Traverse Jay H, Lai Dejian, Pepine Carl J, Taylor Doris A
Regenerative Medicine Department, Texas Heart Institute, Houston, TX, United States.
Stem Cell Center, Texas Heart Institute, Houston, TX, United States.
Front Cardiovasc Med. 2021 Sep 3;8:698088. doi: 10.3389/fcvm.2021.698088. eCollection 2021.
Cell therapy trials for heart failure (HF) have shown modest improvement; however, the mechanisms underlying improvement in some patients but not others are not well understood. Although immune cells are important in the course of HF, our understanding of the immune processes in HF is limited. The objective of this study was to evaluate associations between temporal changes in peripheral blood (PB) cell subpopulations and improved outcome in patients with chronic ischemic cardiomyopathy after bone marrow-derived mononuclear cell therapy or placebo in the FOCUS-CCTRN trial. Peripheral blood was collected at days 0, 1, 30, 90, and 180 from consented participants. We used flow cytometry to compare PB populations in patients with the best (cohort 1) or worst functional outcome (cohort 2) in three primary endpoints: left ventricular (LV) ejection fraction, LV end-systolic volume, and maximal oxygen consumption (VO max). A linear mixed model was used to assess changes over time in 32 cell populations. The difference between each time point and baseline was calculated as linear contrast. Compared with cohort 2, patients who improved (cohort 1) had a higher frequency of CD45CD19 B cells at days 0, 1, 90, and 180. CD11B cells increased over baseline at day 1 in both cohorts and remained higher in cohort 2 until day 30. CD45CD133 progenitor cells decreased over baseline at day 30 in cohort 1. We identified specific cell subpopulations associated with improved cardiac function in patients with chronic LV dysfunction. These findings may improve patient selection and prediction of outcomes in cell therapy trials.
心力衰竭（HF）的细胞治疗试验已显示出一定程度的改善；然而，部分患者病情改善而其他患者未改善的潜在机制尚不清楚。尽管免疫细胞在HF病程中很重要，但我们对HF免疫过程的了解有限。本研究的目的是在FOCUS-CCTRN试验中，评估慢性缺血性心肌病患者接受骨髓来源的单核细胞治疗或安慰剂治疗后，外周血（PB）细胞亚群的时间变化与改善结局之间的关联。在第0、1、30、90和180天从同意参与的受试者中采集外周血。我们使用流式细胞术比较了三个主要终点中功能结局最佳（队列1）或最差（队列2）的患者的PB群体：左心室（LV）射血分数、LV收缩末期容积和最大耗氧量（VO max）。使用线性混合模型评估32个细胞群体随时间的变化。将每个时间点与基线的差异计算为线性对比。与队列2相比，病情改善的患者（队列1）在第0、1、90和180天的CD45CD19 B细胞频率更高。两个队列中的CD11B细胞在第1天均高于基线水平，并且在队列2中直到第30天一直保持较高水平。队列1中的CD45CD133祖细胞在第30天低于基线水平。我们确定了与慢性LV功能障碍患者心脏功能改善相关的特定细胞亚群。这些发现可能会改善细胞治疗试验中的患者选择和结局预测。
