Genetic manipulation and selection of mouse mesenchymal stem cells for delivery of therapeutic factors in vivo

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) hold great potential as an ex vivo cellular system for delivery of therapeutic proteins to the diseased or damaged central nervous system (CNS). This adult stem cell population has considerable translational potential for autologous transplantation due to lack of ethical concerns, accessibility, multipotent nature, and plasticity. Here we describe a methodology and outline a strategy using lentiviral vectors for producing lines of MSCs hypersecreting neurotrophic growth factors (e.g., brain-derived neurotrophic factor (BDNF) and/or glial cell line-derived neurotrophic factor (GDNF)) together with a reporter protein such as green fluorescent protein (GFP) that may be used for in vitro and in vivo neuroprotection bioassays. This approach provides exciting opportunities for basic research and proof-of-concept studies.