Randomized Controlled Trial

. 2015 Jan 2;116(1):99-107.

doi: 10.1161/CIRCRESAHA.116.304710. Epub 2014 Nov 18.

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial

Robert C Schutt¹, Barry H Trachtenberg¹, John P Cooke¹, Jay H Traverse¹, Timothy D Henry¹, Carl J Pepine¹, James T Willerson¹, Emerson C Perin¹, Stephen G Ellis¹, David X M Zhao¹, Aruni Bhatnagar¹, Brian H Johnstone¹, Dejian Lai¹, Micheline Resende¹, Ray F Ebert¹, Joseph C Wu¹, Shelly L Sayre¹, Aaron Orozco¹, Claudia Zierold¹, Robert D Simari¹, Lem Moyé², Christopher R Cogle¹, Doris A Taylor¹; Cardiovascular Cell Therapy Research Network (CCTRN)

Affiliations

¹ From the Houston Methodist DeBakey Heart and Vascular Center (R.C.S., B.H.T., J.P.C.) and Houston Methodist Research Institute (R.C.S., B.H.T., J.P.C.), TX; Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (J.H.T.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); University of Florida College of Medicine, Gainesville (C.J.P., C.R.C.); Texas Heart Institute, CHI St. Luke's Health, Houston (J.T.W., E.C.P., M.R., A.O., D.A.T.); University of Minnesota School of Medicine, Minneapolis (C.Z.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest, School of Medicine, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (A.B.); Indiana University School of Medicine, Indianapolis (B.H.J.); The University of Texas Health Science Center, School of Public Health, Houston (D.L., S.L.S., L.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.F.E.); Stanford University, School of Medicine, CA (J.C.W.); and Kansas University Medical Center, School of Medicine, Kansas City (R.D.S.).
² From the Houston Methodist DeBakey Heart and Vascular Center (R.C.S., B.H.T., J.P.C.) and Houston Methodist Research Institute (R.C.S., B.H.T., J.P.C.), TX; Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (J.H.T.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); University of Florida College of Medicine, Gainesville (C.J.P., C.R.C.); Texas Heart Institute, CHI St. Luke's Health, Houston (J.T.W., E.C.P., M.R., A.O., D.A.T.); University of Minnesota School of Medicine, Minneapolis (C.Z.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest, School of Medicine, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (A.B.); Indiana University School of Medicine, Indianapolis (B.H.J.); The University of Texas Health Science Center, School of Public Health, Houston (D.L., S.L.S., L.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.F.E.); Stanford University, School of Medicine, CA (J.C.W.); and Kansas University Medical Center, School of Medicine, Kansas City (R.D.S.). Lemmoye@msn.com.

PMID: 25406300
PMCID: PMC4282599
DOI: 10.1161/CIRCRESAHA.116.304710

Randomized Controlled Trial

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial

Robert C Schutt et al. Circ Res. 2015.

. 2015 Jan 2;116(1):99-107.

doi: 10.1161/CIRCRESAHA.116.304710. Epub 2014 Nov 18.

Authors

Affiliations

¹ From the Houston Methodist DeBakey Heart and Vascular Center (R.C.S., B.H.T., J.P.C.) and Houston Methodist Research Institute (R.C.S., B.H.T., J.P.C.), TX; Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (J.H.T.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); University of Florida College of Medicine, Gainesville (C.J.P., C.R.C.); Texas Heart Institute, CHI St. Luke's Health, Houston (J.T.W., E.C.P., M.R., A.O., D.A.T.); University of Minnesota School of Medicine, Minneapolis (C.Z.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest, School of Medicine, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (A.B.); Indiana University School of Medicine, Indianapolis (B.H.J.); The University of Texas Health Science Center, School of Public Health, Houston (D.L., S.L.S., L.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.F.E.); Stanford University, School of Medicine, CA (J.C.W.); and Kansas University Medical Center, School of Medicine, Kansas City (R.D.S.).
² From the Houston Methodist DeBakey Heart and Vascular Center (R.C.S., B.H.T., J.P.C.) and Houston Methodist Research Institute (R.C.S., B.H.T., J.P.C.), TX; Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MN (J.H.T.); Cedars-Sinai Heart Institute, Los Angeles, CA (T.D.H.); University of Florida College of Medicine, Gainesville (C.J.P., C.R.C.); Texas Heart Institute, CHI St. Luke's Health, Houston (J.T.W., E.C.P., M.R., A.O., D.A.T.); University of Minnesota School of Medicine, Minneapolis (C.Z.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest, School of Medicine, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (A.B.); Indiana University School of Medicine, Indianapolis (B.H.J.); The University of Texas Health Science Center, School of Public Health, Houston (D.L., S.L.S., L.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.F.E.); Stanford University, School of Medicine, CA (J.C.W.); and Kansas University Medical Center, School of Medicine, Kansas City (R.D.S.). Lemmoye@msn.com.

PMID: 25406300
PMCID: PMC4282599
DOI: 10.1161/CIRCRESAHA.116.304710

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, selected 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 after ST-segment-elevation-myocardial infarction.

Methods and results: This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) 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 MRI. 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 cardiac MRI 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 colony-forming unit Hill and endothelial-colony forming cell 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 segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation.

Clinical trial registration information url: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

Keywords: acute myocardial infarction; adult stem cell; coronary circulation; regeneration.

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Figures

**Figure 1. Gating strategy used for analyzing CD31⁺ cells and CD31⁺ cell subsets**
A, Representative dot plot showing the gates used to identify BMC populations based on forward scatter (FSC-A) versus side scatter (SSC-A). B, Representative histogram showing CD31⁺ cells within the lymphocyte gate. Blue indicates CD31⁺ cells, and red indicates the isotype control. C, Representative dot plot showing the CD45⁺CD31⁺ cells within the lymphocyte gate. D, Representative dot plot showing the CD45⁺CD31^low subset within the lymphocyte gate (gate for the subset shown in black). Percentages shown in panels B, C, and D are based on the total lymphocyte population. All data presented are from a single patient.

**Figure 2. Individual changes in infarct size between day 3 and the 6-month follow-up for patients stratified by the percentage of CD45⁺CD31^low cells**

See this image and copyright information in PMC

Comment in

Bone good to the heart: bone marrow cell characteristics and cardiac repair after STEMI in the CCTRN TIME cohort.
Picozza M, Pompilio G, Capogrossi MC. Picozza M, et al. Circ Res. 2015 Jan 2;116(1):16-8. doi: 10.1161/CIRCRESAHA.114.305502. Circ Res. 2015. PMID: 25552689 No abstract available.

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Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial

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Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial

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