No abstract

Medulloblastoma (MB) is recognized as comprising four molecular subgroups with distinct transcriptional profiles, clinical features, and outcomes. Previous studies demonstrate that pediatric MBs present with subgroup-specific MRI manifestations. We hypothesized that combination of anatomical localization and conventional features based on MR imaging can predict these subgroups in adult MBs. MR Imaging manifestations of 125 adult patients with MB were analyzed retrospectively based on pre-operative MRI scans. MB molecular subgroups were evaluated by the expression profiling array and immunohistochemistry. A pediatric MB cohort of 60 patients were analyzed for comparison with data of adult patients. Multiple logistic regression analysis revealed that tumor location (P < 0.0001) and pattern of enhancement (P = 0.0048) were significantly correlated with molecular subgroups in adult MBs. Ninety-two percent of adult MBs were correctly predicted by using logistic regression model based on the anatomical localization patterns and pattern of enhancement. Exclusively intra-cerebellar growth, localization in the rostral cerebellum, and no brainstem contact were specific to adult SHH-MBs. Group 4-MBs in adult were characterized by minimal/no enhancement compared with other two subgroups. Infant SHH-MBs represented significant different localization patterns compared with SHH tumors in children and adults. We identified that molecular subgroups of adult MBs could be well predicted by tumor localization patterns and enhancement pattern. Our study also provided important evidence that MB subgroups in adult possibly derived from different cellular origins.

Parkinson’s disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.