PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration

Abstract

Background Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified (GM) MSCs that over-express specific cytokines, growth factors or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine Interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages could potentially enhance osteogenesis by MSC lineage cells. However, IL-4 inhibits osteogenesis during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect. Methods In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected the MSCs with the PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate protein expression, cell proliferation and viability as well as the capability for osteogenesis. Results Co-overexpression of PDGF-BB and IL-4 was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone. Conclusions Thus, overexpression of both PDGF-BB and IL-4 may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.