Detailed Analysis of Bone Marrow From Patients With Ischemic Heart Disease and Left Ventricular Dysfunction BM CD34, CD11b, and Clonogenic Capacity as Biomarkers for Clinical Outcomes

作者：Cogle Christopher R; Wise Elizabeth; Meacham Amy M; Zierold Claudia; Traverse Jay H; Henry Timothy D; Perin Emerson C; Willerson James T; Ellis Stephen G; Carlson Marjorie; Zhao David X M; Bolli Roberto; Cooke John P; Anwaruddin Saif; Bhatnagar Aruni; Cabreira Hansen Maria da Graca; Grant Maria B; Lai Dejian; Moye Lem^*; Ebert Ray F; Olson Rachel E; Sayre Shelly L; Schulman Ivonne H; Bosse Raphael C; Scott Edward W; Simari Robert D; Pepine Carl J

来源：Circulation Research, 2014, 115(10): 867-U152.

DOI：10.1161/CIRCRESAHA.115.304353

• angiogenesis effect
• blood cells
• bone marrow
• myocardial infarction
• stem cells

Rationale: Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche after acute myocardial infarction (AMI). %26lt;br%26gt;Objective: To study the BM composition in patients with IHD and severe left ventricular (LV) dysfunction. %26lt;br%26gt;Methods and Results: BM from 280 patients with IHD and LV dysfunction were analyzed for cell subsets by flow cytometry and colony assays. BM CD34(+) cell percentage was decreased 7 days after AMI (mean of 1.9% versus 2.3%-2.7% in other cohorts; P%26lt;0.05). BM-derived endothelial colonies were significantly decreased (P%26lt;0.05). Increased BM CD11b(+) cells associated with worse LV ejection fraction (LVEF) after AMI (P%26lt;0.05). Increased BM CD34(+) percentage associated with greater improvement in LVEF (+9.9% versus +2.3%; P=0.03, for patients with AMI and +6.6% versus -0.02%; P=0.021 for patients with chronic IHD). In addition, decreased BM CD34(+) percentage in patients with chronic IHD correlated with decrement in LVEF (-2.9% versus +0.7%; P=0.0355). %26lt;br%26gt;Conclusions: In this study, we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34+ cell nadir 7 days after AMI, a negative correlation between CD11b percentage and postinfarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and reversal of comorbid BM impairment.

• 出版日期2014-10-24