Transplantation with Lentivirus-Mediated VEGF-Infected Rat Adipose-Derived Stem Cells through the Fourth Ventricle Ameliorates Clinical and Pathological Features in an Amyotrophic Lateral Sclerosis Murine Model

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively affects motor neurons. Vascular endothelial growth factor (VEGF) and adipose-derived stem cells (ADSCs) have shown therapeutic efficacy in ALS. VEGF has a combinatorial effect on the proliferation and differentiation of ADSCs in vitro;however, its effects in vitro remain unclear. Methods: A method involving transplantation of ADSCs with or without VEGF through the fourth ventricle was used. An ALS mouse model (G93A-SOD1 transgenic mice) was used to explore the effects of this combination therapy on ALS. The onset of ALS and survival times of G93A-SOD1 mice were noted, compromised, motor function was assessed using a rotating rod experiment, and immunohistochemical and Nissl staining were used to assess neuronal changes, particularly motor neurons. The expression levels of key proteins were analyzed by western blotting. Results: The transplantation of GFP-rADSCs and VEGF-rADSCs in G93A-SOD1 mice delayed the onset of ALS, enhanced the survival and motor function of mice, improved the structure and number of neuronal cells, inhibited the hyperplasia of astrocytes, and upregulated the expression of VEGF and glutamate transporter-1 (GLT-1) protein. Conclusions: Combination therapy may protect motor neurons by promoting the expression of VEGF and GLT-1, thereby reducing astrocyte hyperplasia, improving motor function, delaying the onset of ALS, and prolonging the lifespan of G93A-SOD1 mice.