Human MuStem cells repress T-cell proliferation and cytotoxicity through both paracrine and contact-dependent pathways

Background Muscular dystrophies (MDs) are inherited diseases in which a dysregulation of the immune response exacerbates disease severity and are characterized by infiltration of various immune cell types leading to muscle inflammation, fiber necrosis and fibrosis. Immunosuppressive properties have been attributed to mesenchymal stem cells (MSCs) that regulate the phenotype and function of different immune cells. However, such properties were poorly considered until now for adult stem cells with myogenic potential and advanced as possible therapeutic candidates for MDs. In the present study, we investigated the immunoregulatory potential of human MuStem (hMuStem) cells, for which we previously demonstrated that they can survive in injured muscle and robustly counteract adverse tissue remodeling. Methods The impact of hMuStem cells or their secretome on the proliferative and phenotypic properties of T-cells was explored by co-culture experiments with either peripheral blood mononucleated cells or CD3-sorted T-cells. A comparative study was produced with the bone marrow (BM)-MSCs. The expression profile of immune cell-related markers on hMuStem cells was determined by flow cytometry while their secretory profile was examined by ELISA assays. Finally, the paracrine and cell contact-dependent effects of hMuStem cells on the T-cell-mediated cytotoxic response were analyzed through IFN-γ expression and lysis activity. Results Here, we show that hMuStem cells have an immunosuppressive phenotype and can inhibit the proliferation and the cytotoxic response of T-cells as well as promote the generation of regulatory T-cells through direct contact and via soluble factors. These effects are associated, in part, with the production of mediators including heme-oxygenase-1, leukemia inhibitory factor and intracellular cell adhesion molecule-1, all of which are produced at significantly higher levels by hMuStem cells than BM-MSCs. While the production of prostaglandin E2 is involved in the suppression of T-cell proliferation by both hMuStem cells and BM-MSCs, the participation of inducible nitric oxide synthase activity appears to be specific to hMuStem cell-mediated one. Conclusions Together, our findings demonstrate that hMuStem cells are potent immunoregulatory cells. Combined with their myogenic potential, the attribution of these properties reinforces the positioning of hMuStem cells as candidate therapeutic agents for the treatment of MDs.

Case Report: Isolated Idiopathic Saccular Dysfunction

Advances in vestibular testing have now allowed us to test each semicircular canal as well as the utricle and saccule, independently. This has led to the discovery of new patterns of vestibular dysfunction that were once impossible to evaluate. This report describes the case of a 20-year-old woman with a 2-month history of recurrent dizziness. She had a complete audiovestibular assessment. The only abnormality observed was the absence of a cervical vestibular-evoked myogenic potential response for the right side, hence an isolated saccular dysfunction. In conclusion, isolated otolithic dysfunction is probably an overlooked and neglected clinical presentation. Its true incidence is unknown, and further research is needed to understand this clinical entity.

Skull Vibration Induced Nystagmus Test: Correlations with Semicircular Canal and Otolith Asymmetries

Background: To establish in patients with peripheral vestibular disorders relations between skull vibration-induced nystagmus (SVIN) different components (horizontal, vertical, torsional) and the results of different structurally related vestibular tests. Methods: SVIN test, canal vestibular test (CVT: caloric test + video head impulse test: VHIT), otolithic vestibular test (OVT: ocular vestibular evoked myogenic potential oVEMP + cervical vestibular evoked myogenic potential cVEMP) performed on the same day in 52 patients with peripheral vestibular diseases (age < 65 years), and 11 control patients were analyzed. Mixed effects logistic regression analysis was performed to assert whether the presence of nystagmus in SVIN (3D analysis) have an association with the presence of peripheral vestibular dysfunction measured by vestibular explorations (CVT or OVT). Results: We obtained different groups: Group-Co (control group), Group-VNT (dizzy patients with no vestibular tests alterations), Group-O (OVT alterations only), Group-C (CVT alterations only), Group-M (mixed alterations). SVIN-SPV horizontal component was significantly higher in Group-M than in the other groups (p = 0.005) and correlated with alterations of lateral-VHIT (p < 0.001), caloric test (p = 0.002) and oVEMP (p = 0.006). SVIN-SPV vertical component was correlated with the anterior-VHIT and oVEMP alterations (p = 0.007; p = 0.017, respectively). SVIN-SPV torsional component was correlated with the anterior-VHIT positivity (p = 0.017). SVIN was the only positive test for 10% of patients (83% of Group-VNT). Conclusion: SVIN-SPV analysis in dizzy patients shows significant correlation to both CVT and OVT. SVIN horizontal component is mainly relevant to both vestibular tests exploring lateral canal and utricle responses. SVIN-SPV is significantly higher in patients with combined canal and otolith lesions. In some patients with dizziness, SVIN may be the only positive test.

Vestibular System Eletrophysiology: An Analysis of The Relationship between Hearing and Movement

Introduction Knowledge about the positive effects that music and dance bring, in its various forms, to the healthy human brain, is important not only in the context of basic neuroscience but may also strongly affect practices in neurorehabilitation. Objective To verify the relationship between hearing and movement and, specifically, to analyze the interference of professional dance practice and formal musical training in the magnitude of the vestibule-cervical and vestibular reflexes. Method The sample consisted of 92 subjects, aged between 18 and 35 years old, 31 professional musicians, 31 ballet dancers, and 30 control subjects. Only subjects with normal hearing sensitivity were included. Cervical vestibular evoked myogenic potential (cVEMP) was recorded in the sternocleidomastoid muscle, and ocular vestibular evoked myogenic potential (oVEMP) was recorded in the lower oblique muscle of the eye, using tone-bursts (500Hz). Analysis of variance (ANOVA) or Kruskall-Wallis tests were performed. Results The cVEMP presented earlier and higher amplitude waves when recorded in the group of dancers, with a significant difference between all tested groups for latency and amplitude of the N23 wave; the comparison was restricted between dancers and control groups, with no difference between ballet dancers and musicians. The N1 wave of the oVEMP presented lower latencies in dancers than in musicians and controls (p = 0.001). No significant differences were found between the groups for the P1 wave. Conclusion Greater magnitudes of vestibule-cervical reflex responses and faster vestibule-ocular reflex responses were observed in dancers. Dance practice provides greater development of the vestibular system, but musical training also contributes to the magnitude of these responses.