The Mechanisms of Mesenchymal Stem Cells in the Treatment of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is a leading cause of disability in young adults. Most therapeutic strategies are based on immunosuppressant effects. However, none of the drugs showed complete remission and may result in serious adverse events such as infection. Mesenchymal stem cells (MSCs) have gained much attention and are considered a potential therapeutic strategy owing to their immunomodulatory effects and neuroprotective functions. Experimental autoimmune encephalomyelitis (EAE), a classical animal model for MS, is widely used to explore the efficacy and mechanism of MSC transplantation. This review summarises the therapeutic mechanism of MSCs in the treatment of EAE, including the effects on immune cells (T cells, B cells, dendritic cells, natural killer cells) and central nervous system-resident cells (astroglia, microglia, oligodendrocytes, neurons) as well as various strategies to improve the efficacy of MSCs in the treatment of EAE. Additionally, we discuss the clinical application of MSCs for MS patients as well as the challenges and prospects of MSC transplantation.

Obesity-induced oxidative stress and mitochondrial dysfunction negatively affect sperm quality.

Obesity is a systemic metabolic disease that can induce male infertility or subfertility through oxidative stress. The aim of this study was to determine how obesity impairs sperm mitochondrial structural integrity and function, and reduces sperm quality in both overweight/obese men and mice on a high-fat diet (HFD). Mice fed the HFD demonstrated higher body weight and increased abdominal fat content than those fed the control diet. Such effects accompanied the decline in antioxidant enzymes, such as glutathione peroxidase (GPX) and catalase and superoxide dismutase (SOD) in testicular and epidydimal tissues. Moreover, malondialdehyde (MDA) content significantly increased in sera. Mature sperm in HFD mice demonstrated higher oxidative stress, including increased mitochondrial reactive oxygen species (ROS) levels and decreased protein expression of GPX1, which may impair mitochondrial structural integrity and reduce mitochondrial membrane potential (MMP) and ATP production. Moreover, cyclic AMPK phosphorylation status increased, whereas sperm motility declined in the HFD mice. Clinical studies demonstrated that being overweight/obese reduced SOD enzyme activity in the seminal plasma and increased ROS in sperm, accompanied by lower MMP and low-quality sperm. Furthermore, ATP content in the sperm was negatively correlated with increases in the BMI of all clinical subjects. In conclusion, our results suggest that excessive fat intake had similar disruptive effects on sperm mitochondrial structure and function, as well as oxidative stress levels in humans and mice, which in turn induced lower sperm motility. This agreement strengthens the notion that fat-induced increases in ROS and impaired mitochondrial function contribute to male subfertility.

Preclinical Studies on Neural Stem/Progenitor Cell Therapy for Ischemic Stroke: A Systematic Review.

BACKGROUND: Neural stem/progenitor cells (NSPCs) transplantation has been recognized in recent years as an effective strategy for the treatment of ischemic stroke. Several preclinical studies have demonstrated the feasibility, safety, and efficacy of NSPCs therapy. METHODS: We conducted a systematic review of the published literature in Pubmed reporting the use of NSPCs in preclinical studies between 2010 and 2021. Based on the articles reporting data, the key factors affecting efficacy were listed. RESULTS: A total of 71 preclinical studies, including 91 treatment arms, were identified. The results showed that several factors could influence the outcomes of NSPCs transplantation, including the type of donor cells, cell dose, time of administration after stroke, delivery route, and anesthetic. Treatment outcomes were measured by infarct volume, behavioral tests, and molecular and cellular level results. CONCLUSION: Most of the preclinical studies reported statistically significant effects and very few adverse reactions. Transplantation of NSPCs for ischemic stroke still needs to be optimized for several key factors. A standardized treatment outcome assessment could ease the translation of evidence in clinical settings.

Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in NMOSD patients.

Background and objectives: Cerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the 'glymphatic system'. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients. Methods: We conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity. Results: The median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p<0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p<0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5). Discussion: In our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.

Tracking Neural Stem Cells in vivo: Achievements and Limitations.

Neural stem cell (NSC) therapies are developing rapidly and have been proposed as a treatment option for various neurological diseases, such as stroke, Parkinson's disease and multiple sclerosis. However, monitoring transplanted NSCs, exploring their location and migration, and evaluating their efficacy and safety have all become serious and important issues. Two main problems in tracking NSCs have been noted: labeling them for visibility and imaging them. Direct labeling and reporter gene labeling are the two main methods for labeling stem cells. Magnetic resonance imaging and nuclear imaging, including positron emission tomography, single-photon emission computed tomography, and optical imaging, are the most commonly used imaging techniques. Each has its strengths and weaknesses. Thus, multimodal imaging, which combines two or more imaging methods to complement the advantages and disadvantages of each, has garnered increased attention. Advances in image fusion and nanotechnology, as well as the exploration of new tracers and new imaging modalities have substantially facilitated the development of NSC tracking technology. However, the safety issues related to tracking and long-term tracking of cell viability are still challenges. In this review, we discuss the merits and defects of different labeling and imaging methods, as well as recent advances, challenges and prospects in NSC tracking.