Table 1.

Summary of hallmark studies in defining a human EPC.

Year	Lead author	Masker	Method Used to Isolate	Marker to define	Term	Weaknesses of the study	Proposed term
1997	Asahara	CD34 or KDR	Immunomagnetic bead separation of CD34 or KDR positive adult peripheral blood cells	CD45, CD34, CD31, Flk-1, Tie-2 E-selectin, UEA-1, acLDL	EPC	Failed to exclude the presence of hematopoietic cells and no direct demonstration of in vivo vessel forming ability	Proangiogenic hematopoietic cell
2000	Peichev	CD34, AC133, and KDR	Immunomagnetic bead separation of CD34 positive adult peripheral blood cells	CXCR4, CD31, CD13, acLDL, and not CD14 or CD15	CEP	Did not assay for CD45 expression – cells neither form vessels in vitro nor in vivo	Proangiogenic hematopoietic cell
2001	Lin	CD146 (P1H12)	Plating of mononuclear cell pellet or immunomagnetic bead separation of CD146 positive adult peripheral blood cells	CD34, CD144, vWF, Flk-1, and not CD14	BOEC	No evidence for clonal proliferative potential and no direct demonstration of vessel forming ability	BOEC
2003	Hill	Mononuclear cells	48 h pre-plating period prior to replating non-adherent blood mononuclear cells and colony formation 4–9 days later	CD31, Tie2, and KDR	CFU-Hill	Failed to exclude the presence of hematopoietic cells in the colonies and no direct demonstration of vessel forming ability	Pro-angiogenic hematopoietic cell
2004	Ingram	Mononuclear cells	In vitro colony emergence and clonal proliferative potential	CD34, CD146, CD31, CD105, and not CD45 and direct demonstration of vessel formation in vivo	ECFC	Lacks antigen to distinguish ECFC from other circulating EC	ECFC
2007	Rohde	Rohde Mononuclear cells	48 h pre-plating period prior to replating non-adherent blood mononuclear cells and colony formation 4–9 days later	(VEGF-R1, 2, and 3), CD31, CD34, CD146, vWF, and not CD14 CD45	CFU-EC	Could not identify all of the proangiogenic activity related to cultured hematopoietic cells	Proangiogenic hematopoietic cell
2007	Yoder	Mononuclear cells	In vitro colony emergence and clonal proliferative potential and 48 h pre-plating period prior to replating non-adherent blood mononuclear cells and colony formation 4–9 days later	CD34, CD146, CD31, CD105, and not CD45 and direct demonstration of vessel formation in vivo	ECFC Vs. CFUHill	Lacks antigen to distinguish ECFC from other circulating EC	ECFC and Proangiogenic hematopoietic cell
2009	Prokopi	Mononuclear cells	Plating of mononuclear cell pellet on fibronectin-coated dishes and at 72 h removed nonadherent cells	CD31, vWF, UEA-1, CD4, and acLDL	EPC	Lack detailed method for determining the extent of the contaminating platelet proteome to the adherent blood cells	Putative EPC and platelets
2010	Estes	CD34, AC133, CD45, CD31	Polychromatic flow cytometry and cell sorting	CD34, AC133, CD45, CD31	Proangiogenic hematopoietic cell	Lacked detailed examination of contribution of proangiogenic cells to the tumor microvasculature	Proangiogenic hematopoietic cell

UEA-1, Ulex Europeaus agglutinin-1; acLDL, acetylated low density lipoprotein; CEP, circulating endothelial precursor; ECFC, endothelial colony forming cells; BOEC, blood outgrowth endothelial cells; vWF, von Willebrand factor; CFU-EC, colony forming unit-endothelial cell; CFU-Hill, colony forming unit-Hill.