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Circ Res. 2014 Oct 24;115(10):867-74. doi: 10.1161/CIRCRESAHA.115.304353. Epub 2014 Aug 18.

Detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as biomarkers for clinical outcomes.

Author information

1
From the University of Florida College of Medicine, Gainesville (C.R.C., E.W., A.M.M., M.B.G., R.C.B., E.W.S., C.J.P.); University of Minnesota School of Medicine, Minneapolis (C.Z., M.C.); Minneapolis Heart Institute Foundation at Abbott, MN (J.H.T., T.D.H., R.E.O.); Texas Heart Institute, Houston (E.C.P., J.T.W., M.d.G.C.-H., D.A.T.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest Baptist Health, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (R.B., A.B.); Houston Methodist Research Institute, TX (J.P.C.); University of Pennsylvania School of Medicine, Philadelphia (S.A.); University of Texas School of Public Health, Houston (D.L., L.M., S.L.S.); National Heart, Lung and Blood Institute, Bethesda, MD (R.F.E.); University of Miami School of Medicine, FL (I.H.S.), and Mayo Clinic College of Medicine, Rochester, MN (R.D.S.).
2
From the University of Florida College of Medicine, Gainesville (C.R.C., E.W., A.M.M., M.B.G., R.C.B., E.W.S., C.J.P.); University of Minnesota School of Medicine, Minneapolis (C.Z., M.C.); Minneapolis Heart Institute Foundation at Abbott, MN (J.H.T., T.D.H., R.E.O.); Texas Heart Institute, Houston (E.C.P., J.T.W., M.d.G.C.-H., D.A.T.); Cleveland Clinic Foundation, OH (S.G.E.); Wake Forest Baptist Health, Winston-Salem, NC (D.X.M.Z.); University of Louisville, School of Medicine, KY (R.B., A.B.); Houston Methodist Research Institute, TX (J.P.C.); University of Pennsylvania School of Medicine, Philadelphia (S.A.); University of Texas School of Public Health, Houston (D.L., L.M., S.L.S.); National Heart, Lung and Blood Institute, Bethesda, MD (R.F.E.); University of Miami School of Medicine, FL (I.H.S.), and Mayo Clinic College of Medicine, Rochester, MN (R.D.S.). LemMoye@msn.com.

Abstract

RATIONALE:

Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche after acute myocardial infarction (AMI).

OBJECTIVE:

To study the BM composition in patients with IHD and severe left ventricular (LV) dysfunction.

METHODS AND RESULTS:

BM from 280 patients with IHD and LV dysfunction were analyzed for cell subsets by flow cytometry and colony assays. BM CD34(+) cell percentage was decreased 7 days after AMI (mean of 1.9% versus 2.3%-2.7% in other cohorts; P<0.05). BM-derived endothelial colonies were significantly decreased (P<0.05). Increased BM CD11b(+) cells associated with worse LV ejection fraction (LVEF) after AMI (P<0.05). Increased BM CD34(+) percentage associated with greater improvement in LVEF (+9.9% versus +2.3%; P=0.03, for patients with AMI and +6.6% versus -0.02%; P=0.021 for patients with chronic IHD). In addition, decreased BM CD34(+) percentage in patients with chronic IHD correlated with decrement in LVEF (-2.9% versus +0.7%; P=0.0355).

CONCLUSIONS:

In this study, we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34+ cell nadir 7 days after AMI, a negative correlation between CD11b percentage and postinfarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and reversal of comorbid BM impairment.

CLINICAL TRIAL REGISTRATIONS URL:

http://www.clinicaltrials.gov. Unique identifiers: NCT00684021, NCT00684060, and NCT00824005.

KEYWORDS:

angiogenesis effect; blood cells; bone marrow; myocardial infarction; stem cells

PMID:
25136078
PMCID:
PMC4358751
DOI:
10.1161/CIRCRESAHA.115.304353
[Indexed for MEDLINE]
Free PMC Article

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