Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells.

Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is a fast growing and highly heterogeneous tumor, often characterized by the presence of glioblastoma stem cells (GSCs). The plasticity of GSCs results in therapy resistance and impairs anti-tumor immune response by influencing immune cells in the tumor microenvironment (TME). Previously, β-catenin was associated with stemness in GBM as well as with immune escape mechanisms.

Molecular monitoring of glioblastoma's immunogenicity using a combination of Raman spectroscopy and chemometrics.

Raman spectroscopy (RS) has been used as a powerful diagnostic and non-invasive tool in cancer diagnosis as well as in discrimination of cancer and immune cells. In this study RS in combination with chemometrics was applied to cellular Raman spectral data to distinguish the phenotype of T-cells and monocytes after incubation with media conditioned by glioblastoma stem-cells (GSCs) showing different molecular background. For this purpose, genetic modulations of epithelial-to-mesenchymal transition (EMT) process and expression of immunomodulator CD73 were introduced.

Enzymatic Activity of CD73 Modulates Invasion of Gliomas via Epithelial-Mesenchymal Transition-Like Reprogramming.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumour in adulthood. Despite strong research efforts current treatment options have a limited impact on glioma stem-like cells (GSCs) which contribute to GBM formation, progression and chemoresistance. Invasive growth of GSCs is in part associated with epithelial-mesenchymal-like transition (EMT), a mechanism associated with CD73 in several cancers.

Reciprocal regulation of the cholinic phenotype and epithelial-mesenchymal transition in glioblastoma cells.

Glioblastoma (GBM) is the most malignant brain tumor with very limited therapeutic options. Standard multimodal treatments, including surgical resection and combined radio-chemotherapy do not target the most aggressive subtype of glioma cells, brain tumor stem cells (BTSCs). BTSCs are thought to be responsible for tumor initiation, progression, and relapse.

The effect of neurosphere culture conditions on the cellular metabolism of glioma cells.

Malignant gliomas, with an average survival time of 16-19 months after initial diagnosis, account for one of the most lethal tumours overall. Current standards in patient care provide only unsatisfying strategies in diagnostic and treatment for high-grade gliomas. Here we describe metabolic phenomena in the choline and glycine network associated with stem cell culture conditions in the classical glioma cell line U87.

Characterization of a setup to test the impact of high-amplitude pressure waves on living cells.

The impact of pressure waves on cells may provide several possible applications in biology and medicine including the direct killing of tumors, drug delivery or gene transfection. In this study we characterize the physical properties of mechanical pressure waves generated by a nanosecond laser pulse in a setup with well-defined cell culture conditions. To systematically characterize the system on the relevant length and time scales (micrometers and nanoseconds) we use photon Doppler velocimetry (PDV) and obtain velocity profiles of the cell culture vessel at the passage of the pressure wave.

Clinical neurotransplantation protocol for Huntington's and Parkinson's disease.

Purpose: The concept of transplantation of neuronal cells to treat Huntington's and Parkinson's diseases is based on the proven principle that dopaminergic and GABA-ergic progenitor neurons (from the human developing ventral mesencephalon and whole ganglionic eminence) can survive, differentiate and functionally integrate into an allogenic host brain. However, several donor and host-specific variables play a major role in the safety and outcome of this procedure. In this paper, we seek to summarize an updated neural transplantation protocol, based on our institutional experience and many years of collaboration with other neurotransplantation centers.

CD133/CD15 defines distinct cell subpopulations with differential in vitro clonogenic activity and stem cell-related gene expression profile in in vitro propagated glioblastoma multiforme-derived cell line with a PNET-like component.

Glioblastoma multiforme (GBM), as many other solid tumours, contains a subpopulation of cells termed cancer stem-like cells responsible for the initiation and propagation of tumour growth. However, a unique immunophenotype/surface antigen composition for the clear identification of brain tumour stem cells (BTSC) has not yet been found. Here we report a novel code of cell surface markers for the identification of different cell subpopulations in neurospheres derived from a GBM with a primitive neuroectodermal tumour (PNET)-like component (GBM-PNET).

Resistance to hypoxia-induced, BNIP3-mediated cell death contributes to an increase in a CD133-positive cell population in human glioblastomas in vitro.

In addition to intrinsic regulatory mechanisms, brain tumor stemlike cells (BTSCs), a small subpopulation of malignant glial tumor-derived cells, are influenced by environmental factors. Previous reports showed that lowering oxygen tension induced an increase of BTSCs expressing CD133 and other stem cell-related genes and more pronounced clonogenic capacity in vitro. We investigated the mechanisms responsible for hypoxia-dependent induction of CD133-positive BTSCs in glioblastomas.

Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition.

Here we show that activation of the canonical WNT/β-catenin pathway increases the expression of stem cell genes and promotes the migratory and invasive capacity of glioblastoma. Modulation of WNT signaling alters the expression of epithelial-to-mesenchymal transition activators, suggesting a role of this process in the regulation of glioma motility. Using immunohistochemistry in patient-derived glioblastoma samples we showed higher numbers of cells with intranuclear signal for β-catenin in the infiltrating edge of tumor compared to central tumor parenchyma.

Restricted spontaneous in vitro differentiation and region-specific migration of long-term expanded fetal human neural precursor cells after transplantation into the adult rat brain.

Human fetal neural stem/progenitor cells (hNSCs) are investigated for their potential as a cell source for cell-based therapies in neurodegenerative diseases. However, the limited availability of fetal tissue and insufficient understanding of the lineage-dependent pattern of survival, migration, and differentiation following engraftment are still unresolved issues. In the current study hNSCs derived from different brain regions were long-term expanded in vitro to yield proliferating neurospheres giving rise to neurons, astro-, and oligodendroglial cells and assessed for their potential for migration, differentiation, and anatomical integration following intracerebral grafting into rats.

Combined use of BDNF, ascorbic acid, low oxygen, and prolonged differentiation time generates tyrosine hydroxylase-expressing neurons after long-term in vitro expansion of human fetal midbrain precursor cells.

Freshly isolated fetal midbrain neural precursor cells (NPCs) that maintain the potential to differentiate into dopamine (DA) neurons represent a valuable source for cell therapy in Parkinson's disease. However, it is poorly understood why midbrain NPCs lose their dopaminergic differentiation potential after long-term culture. Here we report that human fetal midbrain NPCs can be extensively proliferated with fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF), and leukemia inhibitory factor (LIF) and efficiently differentiated into tyrosine hydroxylase-immunoreactive (TH-ir) neurons.