Abstract

The term “Endothelial progenitor cell” (EPC) has been used to describe multiple cell populations that express endothelial surface makers and promote vascularisation. However, the only population that has all the characteristics of a real “EPC” is the Endothelial Colony Forming Cells (ECFC). ECFC possess clonal proliferative potential, display endothelial and not myeloid cell surface markers, and exhibit pronounced postnatal vascularisation ability in vivo. ECFC have been used to investigate endothelial molecular dysfunction in several diseases, as they give access to endothelial cells from patients in a non-invasive way. ECFC also represent a promising tool for revascularization of damaged tissue. Here we review the translational applications of ECFC research. We discuss studies which have used ECFC to investigate molecular endothelial abnormalities in several diseases and review the evidence supporting the use of ECFC for autologous cell therapy, gene therapy and tissue regeneration. Finally, we discuss ways to improve the therapeutic efficacy of ECFC in clinical applications, as well as the challenges that must be overcome to use ECFC in clinical trials for regenerative approaches.

Highlights

  • The search for endothelial progenitors started in the late 1990s, when Asahara et al reported the existence of circulating cells with endothelial surface markers and repair capacity, and labeled them “endothelial progenitors” [1]

  • Proteomic screening in Endothelial Colony Forming Cells (ECFC) of Hereditary PAH (HPAH) patients with BMPRII mutations compared to healthy control subjects revealed translationally controlled tumor protein as a key mediator of endothelial prosurvival and growth signaling in Pulmonary Arterial Hypertension (PAH) [41]

  • The presence of ECFC colonies was associated with reduced microvascular obstruction, infarct size and left ventricular remodeling, suggesting that circulating ECFC may be a marker of preserved microvascular integrity in patients with acute myocardial infarction (MI) [51]

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Summary

Recent Advances in Endothelial Colony Forming Cells Toward Their

The term “Endothelial progenitor cell” (EPC) has been used to describe multiple cell populations that express endothelial surface makers and promote vascularisation. ECFC possess clonal proliferative potential, display endothelial and not myeloid cell surface markers, and exhibit pronounced postnatal vascularisation ability in vivo. ECFC have been used to investigate endothelial molecular dysfunction in several diseases, as they give access to endothelial cells from patients in a non-invasive way. We review the translational applications of ECFC research. We discuss studies which have used ECFC to investigate molecular endothelial abnormalities in several diseases and review the evidence supporting the use of ECFC for autologous cell therapy, gene therapy and tissue regeneration. We discuss ways to improve the therapeutic efficacy of ECFC in clinical applications, as well as the challenges that must be overcome to use ECFC in clinical trials for regenerative approaches

INTRODUCTION
Clinical Applications of ECFC
ECFC FOR THE INVESTIGATION OF ENDOTHELIAL CELL BIOLOGY IN DISEASE
Hematological Disorders
Ischemic Heart Disease
Chronic Lung Disease in Adults
ECFC FOR AUTOLOGOUS CELL THERAPY FOR VASCULAR REPAIR
ECFC FOR GENE THERAPY
Hemophilia A
ECFC FOR TISSUE BIOENGINEERING
Bioartificial Vascular Structures
Wound Healing
Bone Repair
IMPROVING ECFC THERAPEUTIC EFFICIENCY
Epigenetic Activation
CHALLENGES THAT LIMIT ECFC CLINICAL APPLICATIONS
Replacement of Reagents Derived From Animals
Limited Availability of ECFC
CONCLUSIONS
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