Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

Bone marrow mononuclear cell (BM-MNC) therapy in ST-elevation acute myocardial infarction (STEMI) has no biological inclusion criteria. Here, we analyzed 63 biomarkers and cytokines in baseline plasma samples from 77 STEMI patients treated with BM-MNCs in the TIME and Late-TIME trials as well as 61 STEMI patients treated with placebo. Response to cell therapy was defined by changes in left ventricular ejection fraction, systolic/diastolic volumes, and wall motion indexes. We investigated the clinical value of circulating proteins in outcome prediction using significance testing, partial least squares discriminant analysis, and receiver operating characteristic (ROC) analysis. Responders had higher biomarker levels (76-94% elevated) than non-responders. Several biomarkers had values that differed significantly (P < 0.05) between responders and non-responders including stem cell factor, platelet-derived growth factor, and interleukin-15. We then used these lead candidates for ROC analysis and found multiple biomarkers with values areas under the curve >0.70 including interleukin 15. These biomarkers were not involved in the placebo-treated subjects suggesting that they may have predictive power. We conclude that plasma profiling after STEMI may help identify patients with a greater likelihood of response to cell-based treatment. Prospective trials are needed to assess the predictive value of the circulating biomarkers

Author Correction: Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

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Identification of Bone Marrow Cell Subpopulations Associated With Improved Functional Outcomes in Patients With Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial

In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4(+) BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy-even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials

Asymmetric shallow mantle structure beneath the Hawaiian Swell—evidence from Rayleigh waves recorded by the PLUME network

Author Posting. © The Author(s), 2011. This article is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 187 (2011): 1725–1742, doi:10.1111/j.1365-246X.2011.05238.x.We present models of the 3-D shear velocity structure of the lithosphere and asthenosphere beneath the Hawaiian hotspot and surrounding region. The models are derived from long-period Rayleigh-wave phase velocities that were obtained from the analysis of seismic recordings collected during two year-long deployments for the Hawaiian Plume-Lithosphere Undersea Mantle Experiment. For this experiment, broad-band seismic sensors were deployed at nearly 70 seafloor sites as well as 10 sites on the Hawaiian Islands. Our seismic images result from a two-step inversion of path-averaged dispersion curves using the two-station method. The images reveal an asymmetry in shear velocity structure with respect to the island chain, most notably in the lower lithosphere at depths of 60 km and greater, and in the asthenosphere. An elongated, 100-km-wide and 300-km-long low-velocity anomaly reaches to depths of at least 140 km. At depths of 60 km and shallower, the lowest velocities are found near the northern end of the island of Hawaii. No major velocity anomalies are found to the south or southeast of Hawaii, at any depth. The low-velocity anomaly in the asthenosphere is consistent with an excess temperature of 200–250 °C and partial melt at the level of a few percent by volume, if we assume that compositional variations as a result of melt extraction play a minor role. We also image small-scale low-velocity anomalies within the lithosphere that may be associated with the volcanic fields surrounding the Hawaiian Islands.This research was financed by the National Science Foundation under grants OCE-00-02470 and OCE-00-02819. Markee was partly sponsored by a SIO graduate student fellowship