Specific Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization.

Background: Despite accumulating evidence that proves the pivotal role of endothelial progenitor cells (EPCs) in ischemic neovascularization, the key signaling cascade that regulates functional EPC kinetics remains unclear.

Methods And Results: In this report, we show that inactivation of specific Jagged-1 (Jag-1)-mediated Notch signals leads to inhibition of postnatal vasculogenesis in hindlimb ischemia via impairment of proliferation, survival, differentiation, and mobilization of bone marrow-derived EPCs. Bone marrow-derived EPCs obtained from Jag-1-/- mice, but not Delta-like (Dll)-1-/- mice, demonstrated less therapeutic potential for ischemic neovascularization than EPCs from the wild type.

Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis.

Estrogen has been demonstrated to promote therapeutic reendothelialization after vascular injury by bone marrow (BM)-derived endothelial progenitor cell (EPC) mobilization and phenotypic modulation. We investigated the primary hypothesis that estrogen regulates physiological postnatal vasculogenesis by modulating bioactivity of BM-derived EPCs through the estrogen receptor (ER), in cyclic hormonally regulated endometrial neovascularization. Cultured human EPCs from peripheral blood mononuclear cells (PB-MNCs) disclosed consistent gene expression of ER alpha as well as downregulated gene expressions of ER beta.

Establishment of a functionally active collagen-binding vascular endothelial growth factor fusion protein in situ.

Objective: Tissue regeneration requires both growth factor and extracellular matrix such as collagen, serving as a scaffold for cell growth. We established FNCBD-VEGF121, consisting of the fibronectin collagen-binding domain (FNCBD) and vascular endothelial growth factor (VEGF) 121, and investigated its properties.

Methods And Results: FNCBD-VEGF121 specifically bound to gelatin and type I, II, III, IV, and V collagen.

Endothelial progenitor cells: past, state of the art, and future.

Recent evidences suggest that endothelial progenitor cells (EPCs) derived from bone marrow (BM) contribute to de novo vessel formation in adults occurring as physiological and pathological responses. Emerging preclinical trials have shown that EPCs home to sites of neovascularization after ischemic events in limb and myocardium. On the basis of these aspects, EPCs are expected to develop as a key strategy of therapeutic applications for the ischemic organs.