Neurogenic Potential of Engineered Mesenchymal Stem Cells Overexpressing VEGF

Alan J. Man, Gregory Kujawski, Travis S. Burns, Elaine N. Miller, Fernando A Fierro, Jonathan K Leach, Peter Bannerman

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 explants in 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.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalCellular and Molecular Bioengineering
Volume9
Issue number1
DOIs
StatePublished - Mar 1 2016

Keywords

  • Mesenchymal stem cells
  • Nerve regeneration
  • Peripheral nerve injury
  • VEGF

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Modeling and Simulation

Fingerprint Dive into the research topics of 'Neurogenic Potential of Engineered Mesenchymal Stem Cells Overexpressing VEGF'. Together they form a unique fingerprint.

Cite this