Are Endothelial Progenitor Cells the Real Solution for Cardiovascular Diseases? Focus on Controversies and Perspectives

Table 3

EPCs therapeutic applications.

Preclinical studies in animal models		References
Therapeutic approaches and effects
Animal models
Rat model of myocardial infarction	Intravenous injection of exvivo expanded human CD34^+ cells improves left ventricular function	[46]
Swine model of myocardial infarction	Catheter-based intramyocardial transplantation of EPCs leads to encouraging outcome	[47, 48]
Rat model of diabetes	Infusion of invivo expanded human EPCs augments conduction velocity and blood flow in sciatic nerve	[49]
Rat model of chronic cerebral ischemia	Injection of CD34^+ HSC cells (including EPCs) improves neurological functions	[50]
Macacus rhesus	Skin autograft of CD34^+ cells transfected with recombinant nonreplicative Herpes virus vector results in vector-gene expression and determines an increase in local angiogenesis	[51]
Clinical trials in humans
Pathological CVD conditions
Myocardial infarction	Endovenous administration of G-CSF as mobilizing factor for BM-derived progenitor cells improves left ventricular function	[52]
	Intracoronary infusion of BM-derived progenitor cells improves left ventricular function (TOPCARE-AMI and BOOST trials)	[53–55]
Diffuse coronary heart disease and angina pectoris	Transepicardial and transendocardial injection of unfractioned BM cells improve left ventricular function and physical capacity	[59–62]
Chronic limb ischemia	Direct administration of EPCs determines a reduced rate of limb’s amputation at three-year follow-up	[63, 64]
Autologous EPCs application
Pathological CVD conditions
Chronic limb ischemia	Intramuscular injection of autologous BM-derived mononuclear cells containing 1% of CD34^+ cells determines a local increase in endothelial markers (CD133 and VE-cadherin)	[65, 66]
Symptomatic coronary atherosclerosis	Administration of autologous EPCs expanded for four days in culture improves endothelial function and wall motion abnormalities, showing a benefic effect on the metabolism in the target area	[67]
Chronic limb ischemia	Intramuscular injection of autologous BM mononuclear cells improves local neovascularization (TACT study) and significantly lowers amputation rate at 3-year follow-up	[64]