Endothelial progenitor cells and coronary artery disease: Current concepts and future research directions

Table 1 Clinical studies of endothelial progenitor cell therapy

Ref.	Article	Species	EPCs category	Result
Britten et al[71], 2003	Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): Mechanistic insights from serial contrast-enhanced magnetic resonance imaging	Human	CD34, CD45, CD133	The progenitor cell therapy could rescue dysfunctional myocardium early after AMI
Döbert et al[72], 2004	Transplantation of progenitor cells after reperfused acute myocardial infarction: Evaluation of perfusion and myocardial viability with FDG-PET and thallium SPECT	Human	BMCs and EPCs	The EPC therapy could increase myocardial viability
Wang et al[73], 2007	Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: A pilot randomized controlled trial	Human	Peripheral blood EPCs	Infusion of EPCs seemed to be feasible and safe, and might have beneficially affect to AMI patients
Dedobbeleer et al[74], 2004	Myocardial homing and coronary endothelial function after autologous blood CD34+ progenitor cells intracoronary injection in the chronic phase of myocardial infarction	Human	CD34	The safety and homing ability of EPCs are proved in both acute and chronic conditions
Flores-Ramírez et al[77], 2010	Intracoronary infusion of CD133+ endothelial progenitor cells improves heart function and quality of life in patients with chronic post-infarct heart insufficiency	Human	CD133	The EPCs therapy had improved the heart function of patients
Dubois et al[78], 2010	Differential effects of progenitor cell populations on left ventricular remodeling and myocardial neovascularization after myocardial infarction	Pig	CD31, CD90, CD29, CD44, CD45	Infusion of late-outgrowth EPCs could improve myocardial infarction remodeling
Lee et al[70], 2015	Intracoronary transfusion of circulation-derived CD34+ cells improves left ventricular function in patients with end-stage diffuse coronary artery disease unsuitable for coronary intervention	Human	CD34	CD34+ cell therapy was safe and efficacious in improving heart function
Sung et al[75], 2018	Five-year clinical and angiographic follow-up outcomes of intracoronary transfusion of circulation-derived CD34+ cells for patients with end-stage diffuse coronary artery disease unsuitable for coronary intervention-phase 1 clinical trial	Human	CD34	CD34+ cell therapy might contribute to improving left ventricular function, heart failure, and amelioration of left ventricular remodeling
Shen et al[80], 2018	Induced pluripotent stem cell-derived endothelial progenitor cells attenuate ischemic acute kidney injury and cardiac dysfunction	Mouse	CD31	EPC therapy may reduce the effect of cardiomyocyte apoptosis and cardiac dysfunction
Lee et al[79], 2019	Clinical assessment of intravenous endothelial progenitor cell transplantation in dogs. cell transplant	Dog	CD105, CD31 and CD144	Dogs with EPC transplantation have reduced platelets, increased VEGF, and increased IL-10
Angulski et al[81], 2019	systemic infusion of expanded CD133+ cells and expanded CD133+ cell-derived EVs for the treatment of ischemic cardiomyopathy in a rat model of AMI	Rat	CD133	Not significant effect was observed in this experiment

AMI: Acute myocardial infarction; BMCs: Blood mononuclear cells; EPCs: Endothelial progenitor cells; EV: Extracellular vesicle; SPECT: Single photon emission computed tomography; TOPCARE-AMI: Transplantation of Progenitor Cells and Regeneration Enhancement in AMI; VEGF: Vascular endothelial growth factor.

Table 2 Clinical outcomes with endothelial progenitor cell stents

Ref.	Article	Patients, n	Inclusion criteria	Major clinical outcomes
Sung et al[75], 2018	Five-yr clinical and angiographic follow-up outcomes of intracoronary transfusion of circulation-derived CD34+ cells for patients with end-stage diffuse coronary artery disease unsuitable for coronary intervention phase 1 clinical trial	38	Death from any cause/major adverse cardiac and cerebrovascular event/target vessel revascularization/newly onset atrial fibrillation	Five-yr clinical outcomes: Noncardiovascular death: 13.2%. Cardiovascular death: 7.9%. Acute myocardial infarction: 7.9%. Newly onset atrial fibrillation: 2.6%
Sarno et al[85], 2017	Real-life clinical outcomes with everolimus eluting platinum chromium stent with an abluminal biodegradable polymer in patients from the Swedish coronary angiography and angioplasty registry (SCAAR)	42357	Clinical presentation/lesion characteristics	One-yr outcomes: Restenosis: 1.1%; Restenotic lesion: 3.8%; Death: 5.2%
den Dekker et al[87], 2011	Final results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody-coated stent (Genous stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients	100	Angiographic features/ MACCE rate	Two-yr clinical outcomes: MACCE: 16.6%, MI: 5.2%, TLR clinically driven: 11.5%, TVF: 14.6%, Stent thrombosis: 3.1%
Chandrasekhar et al[88], 2020	1-year COMBO stent outcomes stratified by the PARIS bleeding prediction score: From the MASCOT registry	2279	One-yr TLF/target lesion revascularization/ST/major adverse cardiac events	One-yr outcomes: TLF: 6.7%, Cardiac death: 2.4%, MI: 2.9%, TLR: 3.1%, Stent thrombosis: 1.8%

MACCE: Major adverse cardiac and cerebrovascular events; MI: Myocardial infarction; TLR: Target lesion revascularization; TVF: Target vessel failure; TLF: Target lesion failure.