title: Combinatorial approach for improving the outcome of angiogenic therapy in ischemic tissues.
abstract: Two major populations of endothelial progenitor cells (EPC), namely endothelial colony forming cells (ECFC, or late outgrowth EPC) and circulating angiogenic cells (CAC, or early outgrowth EPC) have been reported to play important roles in vasculogenesis in numerous pathological conditions. However, the poor retention of cells into the ischemic tissue and neovessel fragility are two major flaws that need to be overcome for successful angiogenic therapy. The objective of this study was to explore and exploit the functional properties of EPC populations in order to increase the effectiveness of post-ischemic cell therapy. The results indicate different, still complementary, effects of the two EPC populations on adherence and proliferation of vascular endothelial cells. Matrigel plug assay and mouse hind limb ischemia model showed that concomitant administration of CAC-secreted factors and ECFC resulted in three-fold increase in local cell retention and improved muscle perfusion, vessel maturation and hind limb regeneration, in comparison to either treatment alone. By concluding, factors secreted by CAC co-administered at the time of ECFC transplantation improve tissue regeneration and vascular repair through stabilization of newly-derived blood vessels.
authors.affiliation: Institute of Cellular Biology and Pathology "NicolaeSimionescu", Bucharest, Romania.
authors.forename: G
authors.initials: G
authors.lastname: Odent Grigorescu
authors.affiliation: Institute of Cellular Biology and Pathology "NicolaeSimionescu", Bucharest, Romania.
authors.forename: M B
authors.initials: MB
authors.lastname: Preda
authors.affiliation: University Emergency Hospital, Bucharest, Romania.
authors.forename: E
authors.initials: E
authors.lastname: Radu
authors.affiliation: Institute of Cellular Biology and Pathology "NicolaeSimionescu", Bucharest, Romania.
authors.forename: A-M
authors.initials: AM
authors.lastname: Rosca
authors.affiliation: Institute of Cellular Biology and Pathology "NicolaeSimionescu", Bucharest, Romania.
authors.forename: R
authors.initials: R
authors.lastname: Tutuianu
authors.affiliation: Institute of Cellular Biology and Pathology "NicolaeSimionescu", Bucharest, Romania.
authors.forename: D N
authors.initials: DN
authors.lastname: Mitroi
authors.affiliation: Institute of Cellular Biology and Pathology "NicolaeSimionescu", Bucharest, Romania.
authors.forename: M
authors.initials: M
authors.lastname: Simionescu
authors.affiliation: Institute of Cellular Biology and Pathology "NicolaeSimionescu", Bucharest, Romania. Electronic address: sanda.burlacu@icbp.ro.
authors.forename: A
authors.initials: A
authors.lastname: Burlacu
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000637:transplantation*; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D007797:Laminin / Q000737:chemistry; D051379:Mice; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000737:chemistry; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen
keywords: Angiogenesis; Cell transplant; Endothelial progenitor cells; Secreted factors; Vessel muscularization