Elahy, Mina (2015) Osteogenic Effects of Pigment Epithelium Derived Factor on Mesenchymal Stem Cells. PhD thesis, Victoria University.

Abstract

The field of bone tissue engineering has expanded in the recent decade to meet the increasing need to replace bone tissue in skeletal disease, congenital malformation, trauma, and tumours. Stem cell encapsulation has become a promising method in the future of this field. Alginate is a natural polymer that has been used widely for stem cell transplantation due to its biocompatibility. Pigment epithelium-derived factor (PEDF) is known for its anti-cancer properties due to its anti-angiogenic and anti-proliferative properties, particularly against osteosarcoma, a type of primary bone cancer. This study investigated the osteogenic effect of PEDF on mesenchymal stem cells (MSCs) in monolayer cell cultures and encapsulated in alginate beads in vitro and in vivo. Stem cells were isolated from the bone marrow of mouse long bones, and PEDF was used as an osteogenic supplement to differentiate MSCs to osteoblasts in both monolayers and in alginate beads (3D structure). Differentiation to osteoblasts was evaluated by qualitative and quantitative methods such as immunocytochemistry, mineralisation staining, and immunoblotting for the in vitro part of the study. The in vitro study shows that PEDF can stimulate MSCs to differentiate into osteoblasts in both monolayers and alginate beads. Furthermore, alginate beads containing PEDF degraded significantly in comparison to alginate beads alone, indicating that PEDF could be used as an agent to modify alginate and make it suitable for stem cells to interact and proliferate inside the beads. These results then have been taken further to an in vivo ectopic model. The findings from immunohistochemistry for several bone markers as well as microcomputed tomography (μCT) analysis indicate that PEDF in a physiological dose is able to induce bone formation in vivo with and without co-encapsulation with MSCs. These findings can be useful in order to introduce a new biological model for future use in clinical bone tissue engineering.

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