Abstract

Human cardiac progenitor cells isolated from the same host may have advantages over other sources of stem cells. The aim of this study is to establish a new source of human progenitor cells collected from a waste product, pericardiac effusion fluid, after open-heart surgery in children with congenital heart diseases. The fluid was collected every 24 h for 2 days after surgery in 37 children. Mononuclear cells were isolated and expanded in vitro. These pericardial effusion-derived progenitor cells (PEPCs) exhibiting cardiogenic lineage markers, were highly proliferative and enhanced angiogenesis in vitro. Three weeks after stem cell transplantation into the ischemic heart in mice, cardiac ejection fraction was improved significantly without detectable progenitor cells. Gene expression profiles of the repaired hearts revealed activation of several known repair mechanisms including paracrine effects, cell migration, and angiogenesis. These progenitor cells may have the potential for heart regeneration.

Highlights

  • Despite the recent advances in molecular medicine and health care; cardiac diseases, including both adult and congenital heart diseases, are still the leading cause of morbidity and mortality throughout the world [1]

  • Various cytokines including integrin subunit beta 2 (ITGB2) and matrix metalloproteinase-3 (MMP-3), which have been implicated in promoting angiogenesis and cell migration in the ischemic hearts [26] were increased in the pericardial effusion-derived progenitor cells (PEPCs)-treated group

  • The increased immune complements and chemokine receptors induced by PEPCs at a later time point when PEPCs were physically absent in the ischemic site suggested an enhanced homing or recruitment of host stem cells and other cell types that might contribute to ischemic heart repair [27]

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Summary

Introduction

Despite the recent advances in molecular medicine and health care; cardiac diseases, including both adult and congenital heart diseases, are still the leading cause of morbidity and mortality throughout the world [1]. There are around 1.35 million neonates born with CHD every year over the last 15 years. The prognosis of CHD is good with 83% of patients are free from reoperation for 20 years and the overall survival rate was 86%, including early mortality [5]. CHD patients are at increased risk of developing myocardial ischemia or premature coronary artery disease (CAD) while growing up. The number of adult CHD patients continues to increase by 5% per year, there are more than 1 million patients in the United States [6]. Owing to the lack of effective treatment strategy after severe cardiac injury in these patients, stem cell-based therapies may be a potential therapeutic strategy [7,8]

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