A motif within the N-terminal domain of TSP-1 specifically promotes the proangiogenic activity of endothelial colony-forming cells.

Thrombospondin-1 (TSP-1) gives rise to fragments that have both pro- and anti-angiogenic effects in vitro and in vivo. The TSP-HepI peptide (2.3 kDa), located in the N-terminal domain of TSP-1, has proangiogenic effects on endothelial cells. We have previously shown that TSP-1 itself exhibits a dual effect on endothelial colony-forming cells (ECFC) by enhancing their adhesion through its TSP-HepI fragment while reducing their proliferation and differentiation into vascular tubes (tubulogenesis) in vitro. This effect is likely mediated through CD47 binding to the TSP-1 C-terminal domain. Here we investigated the effect of TSP-HepI peptide on the angiogenic properties of ECFC in vitro and in vivo. TSP-HepI peptide potentiated FGF-2-induced neovascularisation by enhancing ECFC chemotaxis and tubulogenesis in a Matrigel plug assay. ECFC exposure to 20 µg/mL of TSP-HepI peptide for 18 h enhanced cell migration (p < 0.001 versus VEGF exposure), upregulated alpha 6-integrin expression, and enhanced their cell adhesion to activated endothelium under physiological shear stress conditions at levels comparable to those of SDF-1α. The adhesion enhancement appeared to be mediated by the heparan sulfate proteoglycan (HSPG) syndecan-4, as ECFC adhesion was significantly reduced by a syndecan-4-neutralising antibody. ECFC migration and tubulogenesis were stimulated neither by a TSP-HepI peptide with a modified heparin-binding site (S/TSP-HepI) nor when the glycosaminoglycans (GAGs) moieties were removed from the ECFC surface by enzymatic treatment. Ex vivo TSP-HepI priming could potentially serve to enhance the effectiveness of therapeutic neovascularisation with ECFC.

Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke.

AIMS: To assess the safety and feasibility of intra-arterial transplantation of autologous bone marrow mononuclear cells in patients with middle cerebral artery ischemic stroke within 90 days of symptom onset. PATIENTS & METHODS: Six patients were included in the study, and they received 1-5 × 10(8) bone marrow mononuclear cell and were evaluated using blood tests, neurological and imaging examination before treatment, and 1, 3, 7, 30, 60, 90, 120 and 180 days after transplantation. Scintigraphies were carried out 2 and 24 h after the procedure to analyze the biodistribution of labeled cells. Electroencephalogram was conducted within 7 days after transplantation. RESULTS: No patients exhibited any complication or adverse events during the procedure. There was no worsening in the neurological scales until the end of the follow-up. CONCLUSION: Intra-arterial bone marrow mononuclear cell transplantation is feasible and safe in patients with nonacute ischemic strokes of the middle cerebral artery. Further studies are required to evaluate the efficacy of this therapy.