Combined Analysis of Endothelial, Hematopoietic, and Mesenchymal Stem Cell Compartments Shows Simultaneous but Independent Effects of Age and Heart Disease.

Carine Ghem,Renato A K Kalil,Nance Beyer Nardi,Lucinara Dadda Dias,Roberto Tofani Sant’Anna,Melissa Markoski

doi:10.1155/2017/5237634

Abstract

Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays. The study included 36 patients referred for coronary artery bypass grafting or valve replacement surgery. A decreased frequency of stem cells was observed in both groups of patients. Left ventricular dysfunction, diabetes, and intermediate risk in EuroSCORE and SYNTAX score were associated with lower EPCs frequency, and the use of aspirin and β-blockers correlated with a higher frequency of HSCs and EPCs, respectively. Most importantly, the distribution of frequencies in the three stem cell compartments showed independent patterns. The combined investigation of the three stem cell compartments in patients with cardiovascular diseases showed that they are independently affected by the disease, suggesting the investigation of prognostic factors that may be used to determine when autologous stem cells may be used in cell therapy.

Highlights

Cardiovascular disease is one of the major causes of death in the world and requires an extended period of treatment, resulting in high medical costs
This study included patients referred for coronary artery bypass grafting or valve replacement surgery due to ischemic heart disease (IHD) or nonischemic valvular heart disease (VHD), recruited at Institute of Cardiology of Rio Grande do Sul (RS, Brazil) between May 2011 and June 2012
The following associations were observed (Figure 7): lower clonogenic potential for endothelial stem/progenitor cells (EPCs) and Left ventricular (LV) dysfunction (OR = 8.8; 95% CI = 1.69–45.78; p = 0 006), increased frequency of CD34+KDR+ cells and use of aspirin (OR = 0.02; 95% CI = 0.00–0.09; p = 0 022), lower clonogenic potential for hematopoietic stem/progenitor cells (HSCs) and hemoglobin level

Summary

Introduction

Cardiovascular disease is one of the major causes of death in the world and requires an extended period of treatment, resulting in high medical costs. Since the first experimental application of stem cell therapy in heart diseases [1], a very large number of preclinical animal studies have shown that stem/progenitor cells have the ability to improve cardiac function and reduce infarct size, in ischemic as well as nonischemic cardiomyopathy [2, 3]. In spite of reports of effectiveness of cell therapy in heart diseases (reviewed in [4]), the translation of preclinical beneficial results into the clinical setting has been limited. As recently summarized in a systematic review of major randomized controlled cell therapy clinical trials for heart diseases [5], most have proven safe but very limited in clinical efficacy. Despite modest improvements of left ventricular ejection fraction, mortality, reinfarction, or rehospitalization rates were not modified [6]

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