Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs’ mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease.

Many central nervous system (CNS) disorders lack approved treatment options. Previous research demonstrated that peptide CAQK can bind to chondroitin sulfate proteoglycans (CSPGs) in the extracellular matrix of the CNS. In vivo studies have investigated CAQK conjugated to nanoparticles containing therapeutic agents with varying methodologies/outcomes. This paper presents the first systematic review assessing its properties, applications, and outcomes secondary to its use. Following PRISMA guidelines, a comprehensive search was performed across multiple databases. Studies utilizing CAQK as a therapeutic agent/homing molecule in animal/human models were selected. Sixteen studies met the inclusion criteria. Mice and rats were the predominant animal models. All studies except one used CAQK to deliver a therapeutic agent. The reviewed studies mostly included models of brain and spinal cord injuries. Most studies had intravenous administration of CAQK. All studies demonstrated various benefits and that CAQK conjugation facilitated localization to target tissues. No studies directly evaluated the effects of CAQK alone. The data are limited by the heterogeneity in study methodologies and the lack of direct comparison between CAQK and conjugated agents. Overall, these findings present CAQK utilization to deliver a therapeutic agent as a promising targeting strategy in the management of disorders where CSPGs are upregulated.

Background: Cervical spinal cord injuries (SCIs) are the most common type of human SCI. Although various animal SCI contusion models have been developed to mirror human pathology, few have described cervical-level injuries. This study aims to validate and establish optimal impact parameters to produce consistent incomplete cervical SCIs for testing novel therapies. Methods: Using a precise impactor, 3 cervical spinal cord hemi-contusions of varying severities were induced by modifying penetration depths and controlling dwell times. Penetration depths of 2.11 mm (n = 4), 2.24 mm (n = 4), and 2.36 mm (n = 3) were used with a dwell time of 0.05 s to create mild, moderate, and severe injuries. Behavioral assessments in weeks 1, 2, 5, and 8 included grooming test, forelimb asymmetry test, and the Irvine, Beatties, and Bresnahan forelimb scale (IBB). After 8 weeks, rats were euthanized, and spinal cord histology was performed. Results: Within each group, animals exhibited consistent motor deficits and functional recovery. Mean IBB scores varied significantly between each group at week 8 (p < 0.0001). Ipsilateral forelimb usage significantly improved throughout the study period in the mild (2.11 mm) and moderate (2.24 mm) groups, while the severely (2.36 mm) injured group continued to exhibit 100% asymmetrical forelimb usage. Conclusions: This study demonstrates that a precise impactor can create reproducible models of incomplete cervical SCIs. A penetration depth of 2.24 mm resulted in moderate injury with significant motor deficits that slowly improved over time, permitting future therapeutic studies in functional recovery.