Human Umbilical Cord Mesenchymal Stem Cells Derived Exosomes Promote Neurological Function Recovery in a Rat Spinal Cord Injury Model

Abstract

Spinal cord injury (SCI) often leads to personal and social-economic consequences with limited therapeutic options. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSC) have been explored as a promising alternative to cell therapies. In the current study, we explored the mechanism of hUC-MSC derived exosome's ameliorative effect on the spinal cord injury by combining data from in vivo contusion SCI model and in vitro cell viability of PC12 cell line stimulated with lipopolysaccharide. Intravenous administration of hUC-MSC derived exosomes dramatically improved motor function of Sprague-Dawley rats after SCI, with reduced apoptosis demonstrated by increased expression of B-cell lymphoma 2 (BCL2), decreased BCL2 associated X, apoptosis regulator (Bax), and reduced cleaved caspase 9. Conversely, exosome treatment reduced the transcription levels of astrocytes marker GFAP and microglia marker IBA1, suggesting a reduced inflammatory state from SCI injury. Furthermore, exosome treatment in vitro increased the cell viability of PC12 cells. Exosome application activated the Wnt/β-Catenin signaling in the spinal cord. Our study demonstrated that hUC-MSC derived exosomes could improve motor function through anti-apoptosis and anti-inflammatory effects. BCL2/Bax and Wnt/β-catenin signaling pathways were involved in the SCI process and could potentially mediate the protective effect of hUC-MSC derived exosomes.

Keywords: Apoptosis; Exosome; Spinal cord injury; Wnt signaling pathway; hUC-MSC.