The Impact of the Capability of Circulating Progenitor Cell to Differentiate on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction

Abstract

Background-Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI. Methods and Results-Consecutive 51 patients (age, 61Ϯ8 years, meanϮSD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45 low , CD34 ϩ , CD133 ϩ , and VEGFR2 ϩ was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off valueϭmedian). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (nϭ26) and nondifferentiated group (nϭ25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (Pϭ0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of 123 I-BMIPP in the acute phase and 99m Tc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (Pϭ0.0091), decrease in end-systolic volume (Pϭ0.012), and recovery of ejection fraction (Pϭ0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group. Conclusions-In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.

Mobilization of stem and progenitor cells in cardiovascular diseases

“…3,8,10 Moreover, not only the number of EPCs, but also their capability to differentiate into adult endothelial cells may affect functional improvement and infarct size reduction evidenced by nuclear scan, left ventricular ejection fraction salvage and favorable remodeling in patients with AMI. 47 The mobilization of EPCs 24 h after acute MI showed significant positive correlation with extent of viable ischemic myocardium, but not with infarct size and microvascular obstruction. This supports the hypothesis that myocardial ischemia, and not necrosis, is a pivotal determinant of EPCs release from the BM.…”

Mobilized Muse Cells After Acute Myocardial Infarction Predict Cardiac Function and Remodeling in the Chronic Phase

“…18 Another study of AMI patients reported that the number of mobilized EPCs in the peripheral blood and the potential of those EPCs to differentiate into endothelial cells correlated with greater myocardial salvage, decreased end-systolic volume, and increased EF recovery 6 months after AMI. 24 Based on these reports, the main contribution of CD34 + cells and EPCs to AMI is considered neovascularization. [17][18][19] In animal models other than AMI, Muse cells have been shown to home into damaged tissue and differentiate spontaneously into cells compatible with the tissue they targeted and repair damaged tissue.…”

Immunomodulation by Mesenchymal Stem Cells

“…A limited but growing number of follow-up studies involving MSCs have been reported since, most aimed at taking advantage of the plasticity of MSCs to treat a disease. These clinical studies (Table 3) have demonstrated promising results in treating patients with cancer, in reducing the incidence of GVHD after bone marrow transplantation, in promoting heart tissue recovery from massive myocardial infarction, in improving the recovery of patients after amyotrophic lateral sclerosis, and in treating fatal disorders such as metachromatic leukodystrophy and Hurler syndrome (47,(51)(52)(53). At the time of this Perspectives in Diabetes article's submission, ϳ32 clinical trials involving administration of MSCs were listed at http://www.ClinicalTrials.gov, each potentially seeking to exploit the immunomodulatory properties of MSCs to achieve their desired therapeutic goal.…”