Abstract 5050: Wnt11 Enhances Mesenchymal Stem Cells Mediated Angiogenesis via Paracrine Signaling

Abstract

Neovascularization is essential for an organ repair. It has been previously reported that MSC transfected with Wnt11 (MSC Wnt11 ) promotes ischemic heart repair through protecting native cardiomyocytes. However, the mechanism of cardioprotection of MSC Wnt11 remains unknown. Here, it is hypothesized that Wnt11 may enhance MSC mediated angiogenesis via the paracrine effects. Methods: MSCs were isolated from bone marrow of rats and transfected with Wnt11 using Clontech pMSCV retroviral expression system. MSCs transfected with GFP (MSC GFP ) were used as control. MSC (2×10 6 /50 μ l) were transplanted into the border area of ischemic rat hearts which have already underwent left anterior descending coronary artery (LAD) ligation. Four weeks post LAD ligation, regional myocardial blood flow in the ischemic and border zone was evaluated with a colored microsphere technique. The blood vessels were stained with von Willebrand factor (vWF) and counted in peri-infarct regions. Spontaneous capillary-like structure formation was monitored with Gelatin-coated Cytodex 3 microcarrier beads. The expression of growth factors was assayed by microarray and ELISA. Results: The blood flow was significantly increased and the density of blood vessel was higher in MSC Wnt11 transplanted heart than that in MSC GFP transplanted hearts (Fig. A, B ). Microcarrier beads were completely covered by MSC Wnt11 and formed a confluent monolayer and sprouts than MSC GFP (Fig. C ). Growth factors were highly expressed in MSC Wnt11 (Table and Fig. D ). Conclusions: Wnt11 promotes MSC mediated angiogenesis via up-regulating paracrine factors.