Circulating Biomarkers to Identify Responders in Cardiac Cell therapy

Jesse V. Jokerst, Nicholas Cauwenberghs, Tatiana Kuznetsova, Francois Haddad, Timothy Sweeney, Jiayi Hou, Yael Rosenberg-Hasson, Eric Zhao, Robert Schutt, Roberto Bolli, Jay H. Traverse, Carl J. Pepine, Timothy D. Henry, Ivonne H. Schulman, Lem Moyé, Doris A. Taylor, Phillip C. Yang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number4419
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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    Jokerst, J. V., Cauwenberghs, N., Kuznetsova, T., Haddad, F., Sweeney, T., Hou, J., Rosenberg-Hasson, Y., Zhao, E., Schutt, R., Bolli, R., Traverse, J. H., Pepine, C. J., Henry, T. D., Schulman, I. H., Moyé, L., Taylor, D. A., & Yang, P. C. (2017). Circulating Biomarkers to Identify Responders in Cardiac Cell therapy. Scientific reports, 7(1), [4419]. https://doi.org/10.1038/s41598-017-04801-7