Abstract 5050: Wnt11 Enhances Mesenchymal Stem Cells Mediated Angiogenesis via Paracrine Signaling
Neovascularization is essential for an organ repair. It has been previously reported that MSC transfected with Wnt11 (MSCWnt11) promotes ischemic heart repair through protecting native cardiomyocytes. However, the mechanism of cardioprotection of MSCWnt11 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 (MSCGFP) were used as control. MSC (2×106/50μl) 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 MSCWnt11 transplanted heart than that in MSCGFP transplanted hearts (Fig. A, B⇓). Microcarrier beads were completely covered by MSCWnt11 and formed a confluent monolayer and sprouts than MSCGFP (Fig. C⇓). Growth factors were highly expressed in MSCWnt11 (Table⇓ and Fig. D⇓).
Conclusions: Wnt11 promotes MSC mediated angiogenesis via up-regulating paracrine factors.