title: Neurogenic potential of engineered mesenchymal stem cells overexpressing VEGF.
abstract: Numerous signaling molecules are altered following nerve injury, serving as a blueprint for drug delivery approaches that promote nerve repair. However, challenges with achieving the appropriate temporal duration of recombinant protein delivery have limited the therapeutic success of this approach. Genetic engineering of mesenchymal stem cells (MSCs) to enhance the secretion of proangiogenic molecules such as vascular endothelial growth factor (VEGF) may provide an alternative. We hypothesized that the administration of VEGF-expressing human MSCs would stimulate neurite outgrowth and proliferation of cell-types involved in neural repair. When cultured with dorsal root ganglion (DRG) explantsin vitro, control and VEGF-expressing MSCs (VEGF-MSCs) increased neurite extension and proliferation of Schwann cells (SCs) and endothelial cells, while VEGF-MSCs stimulated significantly greater proliferation of endothelial cells. When embedded within a 3D fibrin matrix, VEGF-MSCs maintained overexpression and expressed detectable levels over 21 days. After transplantation into a murine sciatic nerve injury model, VEGF-MSCs maintained high VEGF levels for 2 weeks. This study provides new insight into the role of VEGF on peripheral nerve injury and the viability of transplanted genetically engineered MSCs. The study aims to provide a framework for future studies with the ultimate goal of developing an improved therapy for nerve repair.
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, CA 95817; Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Man
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, CA 95817.
authors.forename: Gregory
authors.initials: G
authors.lastname: Kujawski
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, CA 95817.
authors.forename: Travis S
authors.initials: TS
authors.lastname: Burns
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, CA 95817.
authors.forename: Elaine N
authors.initials: EN
authors.lastname: Miller
authors.affiliation: Institute of Regenerative Cures, University of California, Davis, Sacramento, CA 95817.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Fierro
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616.
authors.forename: J Kent
authors.initials: JK
authors.lastname: Leach
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, CA 95817; Department of Cell Biology, UC Davis School of Medicine, UC Davis Medical Center, Sacramento, CA 95817.
authors.forename: Peter
authors.initials: P
authors.lastname: Bannerman
keywords: Mesenchymal stem cells; Nerve regeneration; Peripheral nerve injury; VEGF