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Identification of cardiovascular risk factors associated with bone marrow cell subsets in patients with STEMI: a biorepository evaluation from the CCTRN TIME and LateTIME clinical trials

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Abstract

Autologous bone marrow mononuclear cell (BM-MNC) therapy for patients with ST-segment elevation myocardial infarction (STEMI) has produced inconsistent results, possibly due to BM-MNC product heterogeneity. Patient-specific cardiovascular risk factors (CRFs) may contribute to variations in BM-MNC composition. We sought to identify associations between BM-MNC subset frequencies and specific CRFs in STEMI patients. Bone marrow was collected from 191 STEMI patients enrolled in the CCTRN TIME and LateTIME trials. Relationships between BM-MNC subsets and CRFs were determined with multivariate analyses. An assessment of CRFs showed that hyperlipidemia and hypertension were associated with a higher frequency of CD11b+ cells (P = 0.045 and P = 0.016, respectively). In addition, we found that females had lower frequencies of CD11b+ (P = 0.018) and CD45+CD14+ (P = 0.028) cells than males, age was inversely associated with the frequency of CD45+CD31+ cells (P = 0.001), smoking was associated with a decreased frequency of CD45+CD31+ cells (P = 0.013), glucose level was positively associated with the frequency of CD45+CD3+ cells, and creatinine level (an indicator of renal function) was inversely associated with the frequency of CD45+CD3+ cells (P = 0.015). In conclusion, the frequencies of monocytic, lymphocytic, and angiogenic BM-MNCs varied in relation to patients’ CRFs. These phenotypic variations may affect cell therapy outcomes and might be an important consideration when selecting patients for and reviewing results from autologous cell therapy trials.

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Abbreviations

BM:

Bone marrow

BM-MNC:

Bone marrow mononuclear cell

CCTRN:

Cardiovascular cell therapy research network

CRF:

Cardiovascular risk factor

IHD:

Ischemic heart disease

LVEF:

Left ventricular ejection fraction

MI:

Myocardial infarction

STEMI:

ST-segment elevation myocardial infarction

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Acknowledgements

We would like to acknowledge the National Heart, Lung, and Blood Institute, and National Center for Research Resources. The CCTRN acknowledges its industry partners, Biosafe, Biologics Delivery System Group, and Cordis Corporation, for their contributions of equipment and technical support during the conduct of the trial. Finally, we would like to thank Heather Leibrecht for her assistance in the preparation of this manuscript.

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    Authors and Affiliations

    1. Texas Heart Institute, Houston, TX, USA

      Ariadna Contreras, Aaron F. Orozco, Micheline Resende, Emerson C. Perin, James T. Willerson & Doris A. Taylor

    2. Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Research Institute, Houston, TX, USA

      Robert C. Schutt & John P. Cooke

    3. Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, MN, USA

      Jay H. Traverse

    4. Cedars Sinai Institute, Los Angeles, CA, USA

      Timothy D. Henry

    5. UT Health School of Public Health, Houston, TX, USA

      Dejian Lai, Michelle L. Cohen & Lem Moyé

    6. University of Louisville, Louisville, KY, USA

      Roberto Bolli

    7. College of Medicine, University of Florida, Gainesville, FL, USA

      Carl J. Pepine

    8. Stanford University School of Medicine, Stanford, CA, USA

      Phillip C. Yang

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    1. Ariadna Contreras
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    For the Cardiovascular Cell Therapy Research Network (CCTRN)

    Corresponding author

    Correspondence to Lem Moyé.

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    There are no potential conflicts of interest to disclose.

    Sources of funding

    This work was supported by the National Heart, Lung, and Blood Institute under cooperative agreement 5 UM1 HL087318. It was also supported, in part, by National Heart, Lung, and Blood Institute contracts N01 HB 37164 and HHSN268201000008C, which were awarded to the Molecular and Cellular Therapeutics Facility, University of Minnesota, and by contracts N01 HB 37163 and HHSN268201000007C, which were awarded to the Cell Processing Facility, Baylor College of Medicine. Further funding provided by National Center for Research Resources CTSA Grant UL1 TR000064 awarded to the University of Florida. In addition, funding from the Texas State Legislature was used to assist investigators at the Texas Heart Institute, Houston, Texas.

    Additional information

    A. Contreras and A. Orozco contributed equally to this work.

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    Contreras, A., Orozco, A.F., Resende, M. et al. Identification of cardiovascular risk factors associated with bone marrow cell subsets in patients with STEMI: a biorepository evaluation from the CCTRN TIME and LateTIME clinical trials. Basic Res Cardiol 112, 3 (2017). https://doi.org/10.1007/s00395-016-0592-z

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