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Sci Rep. 2017 Jun 30;7(1):4419. doi: 10.1038/s41598-017-04801-7.

Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

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Department of NanoEngineering, University of California, San Diego, USA.
Research Unit of Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Department of Medicine, Stanford University, Stanford, USA.
Clinical and Translational Research Institute, University of California, San Diego, USA.
Department of NanoEngineering, University of California, San Diego, USA.
Houston Methodist Hospital, Houston, USA.
School of Medicine, University of Louisville, Louisville, USA.
Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, USA.
University of Florida College of Medicine, Gainesville, USA.
Cedars-Sinai Heart Institute, Los Angeles, USA.
Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, USA.
University of Texas School of Public Health, University of Texas Health Science Center, Houston, USA.
Texas Heart Institute, CHI St. Luke's Health Baylor College of Medicine Medical Center, Houston, USA.


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.

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