Impact of intravenously administered cranial bone-derived mesenchymal stem cells on functional recovery in experimental spinal cord injury

Abstract

Impairments of the central nervous system, such as stroke, brain trauma, and spinal cord injury (SCI), cannot be reversed using current treatment options. Herein, we compared the characteristics of rat cranial bone-derived mesenchymal stem cells (rcMSCs) and rat bone marrow-derived mesenchymal stem cells (rbMSCs). We also investigated the therapeutic effects of intravenously administered rcMSCs and rbMSCs in a rat model of cervical SCI (cSCI) and elucidated its undrelying mechanism. Comprehensive comparative bioinformatics analysis of rcMSCs and rbMSCs RNA sequencing revealed that genes associated with leukocyte transendothelial migration and chemokine signaling were significantly downregulated in rcMSCs. Rats were divided into three groups that received intrtravenous administration of rcMSC, rbMSC, or phosphate-buffered saline (control) 24 h after cSCI. The rcMSC-treated group showed improved functional recovery over the rbMSC-treated and control groups, and reduced lesion volume compared with the control group. The mRNA expression of nitric oxide synthase 2 at the spinal cord lesion site was significantly higher in the rcMSC-treated group than in the control and rbMSCs-treated groups, whereas that of transforming growth factor-β was significantly higher in the rcMSC-treated group compared to that in the control group. The transcriptome data indicated that rcMSCs and rbMSCs differentially affect inflammation. The intravenous administration of rcMSCs contributed to functional recovery and lesion reduction in cSCI. The rcMSCs have the potential to induce an anti-inflammatory environment in cSCI.