Bone marrow mesenchymal stromal cells stimulate skeletal myoblast proliferation through the paracrine release of VEGF.

Mesenchymal stromal cells (MSCs) are the leading cell candidates in the field of regenerative medicine. These cells have also been successfully used to improve skeletal muscle repair/regeneration; however, the mechanisms responsible for their beneficial effects remain to be clarified. On this basis, in the present study, we evaluated in a co-culture system, the ability of bone-marrow MSCs to influence C2C12 myoblast behavior and analyzed the cross-talk between the two cell types at the cellular and molecular level. We found that myoblast proliferation was greatly enhanced in the co-culture as judged by time lapse videomicroscopy, cyclin A expression and EdU incorporation. Moreover, myoblasts immunomagnetically separated from MSCs after co-culture expressed higher mRNA and protein levels of Notch-1, a key determinant of myoblast activation and proliferation, as compared with the single culture. Notch-1 intracellular domain and nuclear localization of Hes-1, a Notch-1 target gene, were also increased in the co-culture. Interestingly, the myoblastic response was mainly dependent on the paracrine release of vascular endothelial growth factor (VEGF) by MSCs. Indeed, the addition of MSC-derived conditioned medium (CM) to C2C12 cells yielded similar results as those observed in the co-culture and increased the phosphorylation and expression levels of VEGFR. The treatment with the selective pharmacological VEGFR inhibitor, KRN633, resulted in a marked attenuation of the receptor activation and concomitantly inhibited the effects of MSC-CM on C2C12 cell growth and Notch-1 signaling. In conclusion, this study provides novel evidence for a role of MSCs in stimulating myoblast cell proliferation and suggests that the functional interaction between the two cell types may be exploited for the development of new and more efficient cell-based skeletal muscle repair strategies

The Role of chimeric antigen receptor T‐cell therapy in immune‐mediated neurological diseases

Despite the use of ‘high efficacy’ disease‐modifying therapies, disease activity and clinical progression of different immune‐mediated neurological diseases continue for some patients, resulting in accumulating disability, deteriorating social and mental health, and high economic cost to patients and society. Although autologous hematopoietic stem cell transplant is an effective treatment modality, it is an intensive chemotherapy‐based therapy with a range of short‐ and long‐term side‐effects. Chimeric antigen receptor T‐cell therapy (CAR‐T) has revolutionized the treatment of B‐cell and other hematological malignancies, conferring long‐term remission for otherwise refractory diseases. However, the toxicity of this treatment, particularly cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome, and the complexity of production necessitate the need for a high level of specialization at treating centers. Early‐phase trials of CAR‐T therapies in immune‐mediated B cell driven conditions, such as systemic lupus erythematosus, neuromyelitis optica spectrum disorder and myasthenia gravis, have shown dramatic clinical response with few adverse events. Based on the common physiopathology, CAR‐T therapy in other immune‐mediated neurological disease, including multiple sclerosis, chronic inflammatory polyradiculopathy, autoimmune encephalitis, and stiff person syndrome, might be an effective option for patients, avoiding the need for long‐term immunosuppressant medications. It may prove to be a more selective immunoablative approach than autologous hematopoietic stem cell transplant, with potentially increased efficacy and lower adverse events. In this review, we present the state of the art and future directions of the use of CAR‐T in such conditions. ANN NEUROL 202

A Cross-Cultural Comparison on Implicit and Explicit Attitudes Towards Artificial Agents

Historically, there has been a great deal of confusion in the literature regarding cross-cultural differences in attitudes towards artificial agents and preferences for their physical appearance. Previous studies have almost exclusively assessed attitudes using self-report measures (i.e., questionnaires). In the present study, we sought to expand our knowledge on the influence of cultural background on explicit and implicit attitudes towards robots and avatars. Using the Negative Attitudes Towards Robots Scale and the Implicit Association Test in a Japanese and Dutch sample, we investigated the effect of culture and robots’ body types on explicit and implicit attitudes across two experiments (total n = 669). Partly overlapping with our hypothesis, we found that Japanese individuals had a more positive explicit attitude towards robots compared to Dutch individuals, but no evidence of such a difference was found at the implicit level. As predicted, the implicit preference towards humans was moderate in both cultural groups, but in contrast to what we expected, neither culture nor robot embodiment influenced this preference. These results suggest that only at the explicit but not implicit level, cultural differences appear in attitudes towards robots

Inhibition of Immune Synapse by Altered Dendritic Cell Actin Distribution: A New Pathway of Mesenchymal Stem Cell Immune Regulation

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Increase in FOXP3+ Regulatory T Cells in GVHD Skin Biopsies Is Associated with Lower Disease Severity and Treatment Response

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Automating outcome analysis after stem cell transplantation: the YORT tool

Hematopoietic stem cell transplantation is a high-risk procedure. Auditing and yearly outcome reviews help keep optimal quality of care and come with increased survival, but also has significant recurring costs. When data has been entered in a standardized registry, outcome analyses can be automated, which reduces work and increases standardization of performed analyses. To achieve this, we created the Yearly Outcome Review Tool (YORT), an offline, graphical tool that gets data from a single center EBMT registry export, allows the user to define filters and groups, and performs standardized analyses for overall survival, event-free survival, engraftment, relapse rate and non-relapse mortality, complications including acute and chronic Graft vs Host Disease (GvHD), and data completeness. YORT allows users to export data as analyzed to allow you to check data and perform manual analyses. We show the use of this tool on a two-year single-center pediatric cohort, demonstrating how the results for both overall and event-free survival and engraftment can be visualized. The current work demonstrates that using registry data, standardized tools can be made to analyze this data, which allows users to perform outcome reviews for local and accreditation purposes graphically with minimal effort, and help perform detailed standardized analyses. The tool is extensible to be able to accommodate future changes in outcome review and center-specific extensions.Transplantation and immunomodulatio