Diffuse and persistent blood–spinal cord barrier disruption after contusive spinal cord injury rapidly recovers following intravenous infusion of bone marrow mesenchymal stem cells

• Published in: Experimental neurology Vol. 267; pp. 152 - 164
• Main Authors: Matsushita, Takashi, Lankford, Karen L., Arroyo, Edgardo J., Sasaki, Masanori, Neyazi, Milad, Radtke, Christine, Kocsis, Jeffery D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2015
• Subjects: Animals; Antigens, Surface - metabolism; Blood spinal cord barrier; Blood-Brain Barrier - physiopathology; Cell- and Tissue-Based Therapy; Disease Models, Animal; Endothelial Cells - pathology; Exploratory Behavior; Glial Fibrillary Acidic Protein - metabolism; Locomotion - physiology; Male; Mesenchymal stem cell; Mesenchymal Stromal Cells - physiology; Microvessels - pathology; Pericytes; Permeability; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Receptor, Platelet-Derived Growth Factor beta - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - therapy; Spinal cord injury; Time Factors; von Willebrand Factor - metabolism; Mesenchymal stem cell; Pericytes; Spinal cord injury; Blood spinal cord barrier
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2015.03.001

Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to reduce the severity of experimental spinal cord injury (SCI), but mechanisms are not fully understood. One important consequence of SCI is damage to the microvasculature and disruption of the blood spinal cord barrier (BSCB). In the present study we induced a contusive SCI at T9 in the rat and studied the effects of intravenous MSC infusion on BSCB permeability, microvascular architecture and locomotor recovery over a 10week period. Intravenously delivered MSCs could not be identified in the spinal cord, but distributed primarily to the lungs where they survived for a couple of days. Spatial and temporal changes in BSCB integrity were assessed by intravenous infusions of Evans blue (EvB) with in vivo and ex vivo optical imaging and spectrophotometric quantitation of EvB leakage into the parenchyma. SCI resulted in prolonged BSCB leakage that was most severe at the impact site but disseminated extensively rostral and caudal to the lesion over 6weeks. Contused spinal cords also showed an increase in vessel size, reduced vessel number, dissociation of pericytes from microvessels and decreases in von Willebrand factor (vWF) and endothelial barrier antigen (EBA) expression. In MSC-treated rats, BSCB leakage was reduced, vWF expression was increased and locomotor function improved beginning 1 week post-MSC infusion, i.e., 2weeks post-SCI. These results suggest that intravenously delivered MSCs have important effects on reducing BSCB leakage which could contribute to their therapeutic efficacy. [Display omitted] •We examined the effects of i.v. MSCs on BSCB & locomotor function after SCI.•Evans blue leakage post contusion was biphasic with a delayed distal response.•I.V. MSC infusion rapidly reduced dye leakage and improved locomotor recovery.•I.V. MSCs did not home to the cord, but trafficked transiently to the lungs.•Recovery of von Willebrand expression correlated with recovery of dye exclusion.