Intravenous administration of human chorionic membrane mesenchymal stem cells promotes functional recovery in a rat traumatic brain injury model

Abstract

Human chorionic membrane mesenchymal stem cells (hCM-MSCs) have increasingly emerged as an excellent source of transplanted cells for regenerative therapy as they can be isolated via a non-invasive and simple method with high proliferative capabilities. However, the roles and mechanisms of hCM-MSCs on traumatic brain injury (TBI) animal models have not been investigated yet. The aim of this study was to investigate the therapeutic potential and mechanism of hCM-MSCs transplantation in a rat model of TBI. Adult male Sprague–Dawley rats were subjected to moderate lateral fluid percussion-induced TBI. At 2 h after TBI, hCM-MSCs, or PBS were administered intravenously via the tail vein. Neurological function, brain water content, Evans blue dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were evaluated. The results showed that transplanted hCM-MSCs were observed in the injured brain. Compared with the PBS group, hCM-MSCs treatment significantly decreased the numbers of M1 macrophages/microglia, MPO+ neutrophils and caspase-3+ cells (P < 0.01). Meanwhile, hCM-MSCs treatment significantly reduced the expression levels of the pro-inflammatory cytokines (TNF-α, interleukin-(IL)6 and IL-1β) while increasing the numbers of M2 macrophages/microglia and the expression of the anti-inflammatory cytokines IL-10 (P < 0.01). In addition, hCM-MSCs treatment significantly reduced brain water content and Evans blue extravasation. Lastly, hCM-MSCs treatment significantly promoted neurogenesis and angiogenesis, and attenuated neurological deficits. Collectively, these findings indicate that hCM-MSCs exhibited effective therapeutic efficacy in a rat TBI model, and its mechanism may be by reducing inflammation, apoptosis and the blood-brain barrier disruption, promoting angiogenesis and neurogenesis.