VEGF-overexpressed Human Tonsil-derived Mesenchymal Stem Cells with PEG/HA-based Cryogels for Therapeutic Angiogenesis

Abstract

Therapeutic neovascularization through cell transplantation has widely been investigated as a cure for ischemia. However, there are several limitations to this technique, including low survival rate of the therapeutic cells and inflammation at the transplanted sites. Polyethylene glycol (PEG)/hyaluronic acid (HA)-based cryogels are used to overcome these problems as they provide cell adhesion sites owing to their interconnected macroporous structure, which increases cell viability in combination with the cryogel's intrinsic biocompatibility. Furthermore, vascular endothelial growth factor (VEGF) plays a significant role in pro-angiogenesis of endothelial cells (ECs) and it has been demonstrated that injection of VEGF-secreting cells could enhance neovascularization at the sites of injection. In the present study, we developed a PEG diacrylate (PEGDA)/glycidyl methacrylate-HA (GMHA)-based cryogel system seeded with VEGF-transfected human tonsil-derived mesenchymal stem cells to induce enhanced neovascularization in murine hind-limb ischemia. Addition of GMHA allowed the PEGDA cryogel to enhance cell metabolism, including attachment and proliferation. The secreted VEGF affected human umbilical vein endothelial cells by enhancing in vitro angiogenesis. Finally, our cell-seeded cryogel successfully facilitated regeneration of blood flow and damaged tissue in a hind-limb ischemia model.