Restoration of Microvascular Function in the Infarct-Related Artery by Intracoronary Transplantation of Bone Marrow Progenitor Cells in Patients With Acute Myocardial Infarction The Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) Trial

Ruhr-Universität Bochum, Bochum, North Rhine-Westphalia, Germany
Circulation (Impact Factor: 14.95). 08/2007; 116(4):366-74. DOI: 10.1161/CIRCULATIONAHA.106.671545
Source: PubMed

ABSTRACT The Doppler Substudy of the randomized, double-blind, placebo-controlled Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial aimed to investigate the effects of intracoronary infusion of bone marrow-derived progenitor cells (BMCs) on coronary blood flow regulation in patients with reperfused acute myocardial infarction.
In a total of 58 patients (BMC group, n=30; placebo group, n=28), coronary flow reserve (CFR) in the infarct artery and a reference vessel was assessed by intracoronary Doppler at the time of study therapy (4.2+/-0.1 days after acute myocardial infarction) and at the 4-month follow-up. Initial CFR was reduced in the infarct artery compared with the reference vessel in both groups (BMC: 2.0+/-0.1 versus 2.9+/-0.2, P<0.05; placebo: 1.9+/-0.1 versus 2.8+/-0.2; P<0.05). At the 4-month follow-up, CFR in the infarct artery had slightly improved in the placebo group (+0.88+/-0.18; P<0.001 versus initial) but was markedly increased by 90% (+1.80+/-0.25; P=0.005 versus placebo) in BMC-treated patients, resulting in a normalization of CFR (3.8+/-0.2; P<0.001 versus initial and placebo at 4 months). In the infarct vessel, adenosine-induced minimal vascular resistance index declined slightly in the placebo group (from 1.77+/-0.12 to 1.52+/-0.15 mm Hg x s/cm; P<0.05) but considerably decreased by -29+/-6% in the BMC group (from 1.86+/-0.19 to 1.20+/-0.12 mm Hg x s/cm; P<0.05 versus initial and placebo at 4 months).
Intracoronary BMC therapy after acute myocardial infarction restores microvascular function of the infarct-related artery, which is associated with a significant improvement in maximal vascular conductance capacity. These data provide clinical proof of concept that progenitor cell transplantation promotes vascular repair.

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Available from: Torsten Tonn, Aug 12, 2015
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    • "Bone marrow–derived endothelial progenitor cells (EPCs) are responsible for neovascularization in postnatal life (Asahara et al. 1999; Takahashi et al. 1999). A large number of reports on EPCs have been accumulated as a potential tool in regenerative medicine (Schachinger et al. 2006a,b; Erbs et al. 2007; Martin- Rendon et al. 2008) or a therapeutic target in oncology (Gao et al. 2008). Although a unique EPC marker has not been identified, EPCs, which most investigators obtain after the in vitro culture, are characterized as cells with high proliferative potential that display typical endothelial characteristics [e.g., expression of endothelial markers and uptake of acetylated lowdensity lipoprotein (Ac-LDL)] and differentiate into ECs in vitro (Timmermans et al. 2009). "
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    • "Indirect assessments can be obtained with conventional measurements of tissue perfusion, such as single-photon emission computed tomography (SPECT) or magnetic-resonance imaging (MRI), but the sensitivity of these techniques is limited. Nevertheless, in a substudy of the REPAIR-AMI (i.e., Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction) trial, intracoronary Doppler measurements indicated that coronary flow reserve in the infarct-related artery was restored 4 months after the infusion of bone-marrow progenitor cells (Erbs et al., 2007), and in our phase 1/ IIa pilot study, positive trends in SPECT perfusion imaging were observed after CD34+ progenitor cells were injected into the hibernating myocardium of patients with chronic angina (Losordo et al., 2007). These trends are further substantiated by findings in our phase IIb ACT34-CMI trial (Losordo et al., 2009). "
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    • "Intracoronary injection of autologous mononuclear bone marrow cells (mBMCs) in patients with acute myocardial infarction (AMI) induces a short-term inflammatory response, which declines after 3 months, as determined by the circulating levels of selected inflammatory markers, suggesting an appropriate window for stem cell transplantation in AMI (Solheim et al., 2008). Intracoronary infusion of bone marrow-derived progenitor cell (BMC) therapy after acute myocardial infarction significantly improves maximal vascular conductance capacity, indicating that implanted BMC promotes vascular repair (Erbs et al., 2007). To address concerns regarding the pro-arrhythmic potential of stem cells, Katritsis et al. (2007) Fig. 4 "
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