Bone Marrow Characteristics Associated With Changes in Infarct Size After STEMI

Abstract

Rationale Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, select patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. Objective The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size following STEMI. Methods and Results This prospective study comprised patients consecutively enrolled in the CCTRN TIME trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac magnetic resonance imaging (cMRI). Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cMRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0%±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31+ BMCs (P=0.046) and in those with faster BMC growth rates in CFU-Hill and ECFC functional assays (P=0.033 and P=0.032, respectively). Conclusions This study identified BMC characteristics associated with a better clinical outcome in patients with STEMI and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these STEMI patients, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. Trial Registration clinicaltrials.gov Identifier: NCT00684021

Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress

“…Regenerative therapies through exogenous stem cell administration hold promising potential [1, 2, 4, 22, 25, 31], but may be limited by excessive cell death after transplantation into an oxidative environment [17]. Since mitochondria are a major source of reactive oxygen species (ROS) in the cell, reductions in mitochondrial metabolism may reduce both the oxidative burden and cell death under oxidative stress.…”

Bone Good to the Heart

“…10,11 It is noteworthy that BM and circulating endothelial cells and monocytes expressing high levels of CD31 have been shown to have proangiogenic and vasculogenic activities 12,13 ; however, in the study by Shutt et al, 1 BM CD31 + cells that exhibit a positive correlation with the decrease in infarct size are lymphocytes (ie, CD45 + CD31 low ). Given that T cells are the major lymphocyte subset in BMC, and that CD31 + T lymphocytes decrease while CD31 -increase during life, 14 the results by Shutt et al 1 of diminished myocardial healing in individuals with low frequency of CD31 + lymphocytes among BMC strengthen the hypothesis that aging of the immune system plays an important role in the lack of myocardial regeneration.…”

“…8 Despite these previous studies on circulating BMC in acute MI, a detailed evaluation of resident BMC in humans with MI was missing. The work by Shutt et al 1 analyzes the cells in the BM of patients with acute MI for their ability to give rise to endothelial, mesenchymal, and proangiogenic cell colonies, assessed in vitro by endothelial colony-forming cells, colonyforming units (CFU)-fibroblasts, and CFU-Hill assays as surrogate markers of the healing potential of regenerative cells. Furthermore, the authors evaluate BMC composition by the use of multiparametric flow cytometry.…”

“…I n this issue of Circulation Research, Shutt et al 1 explore the characteristics of resident bone marrow cells (BMC) in patients enrolled in the Timing In Myocardial infarction Evaluation (TIME) clinical trial, in search of cellular correlates of reduction of the infarcted area 6 months after acute myocardial infarction (MI). The central hypothesis is that endogenous BM properties could affect the clinical outcome.…”

A Look at the Bone Marrow Predicts the Global Outcome

“…2 There is a growing interest in the BM status in patients with cardiovascular disease or risk factors. 11,12 For instance, acute myocardial infarction induces BM metabolic activation, 13 and failure of the BM to mobilize CD34 + cells post-acute myocardial infarction is associated with a poor outcome. 14 In diabetes mellitus, especially with vascular disease, the BM undergoes extensive remodeling and stem cell mobilization is impaired.…”