Abstract The cerebellum plays major role in motor coordination and learning. It contains half of the neurons in the brain. Thus, deciphering the mechanisms by which cerebellar neurons are generated is essential to understand the cerebellar functions and the pathologies associated with it. In a recent study, Wojcinski et al. (2017) by using in vivo Cre/loxP technologies reveal that Nestin‐expressing progenitors repopulated the external granular cell layer after injury. Depletion of postnatal external granular cell layer is not sufficient to induce motor behavior defects in adults, as the cerebellum recovers these neurons. Strikingly, Nestin‐expressing progenitors differentiate into granule cell precursors and mature granule neurons after ablation of perinatal external granular layer, either by irradiation or by genetic ablation. This work identified a novel role of Nestin‐expressing progenitors in the cerebellar microenvironment during development, and revealed that extracellular signals can convert specified progenitors into multipotent stem cells. Here, we discuss the findings from this study, and evaluate recent advances in our understanding of the cerebellar neurogenesis.
Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties
Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.
Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1– 7 (Ang(1– 7)) to reduce vascular compression and deposition of extracellular matrix in mice. Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1– 7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization. Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors. Keywords: immunotherapy, TRAIL, mRNA, lipid nanoparticle, losartan, angiotensin (1– 7)
Inside Front Cover: The cover image is based on the Research Article Nestin and NG2 transgenes reveal two populations of perivascular cells stimulated by photobiomodulation by Alexander Birbrair et al., https://doi.org/10.1002/jcp.30680.
Bone marrow fibrosis is a reactive process, and a central pathological feature of primary myelofibrosis. Revealing the origin of fibroblastic cells in the bone marrow is crucial, as these cells are considered an ideal, and essential target for anti-fibrotic therapy. In 2 recent studies, Decker et al. (2017) and Schneider et al. (2017), by using state-of-the-art techniques including in vivo lineage-tracing, provide evidence that leptin receptor (LepR)-expressing and Gli1-expressing cells are responsible for fibrotic tissue deposition in the bone marrow. However, what is the relationship between these 2 bone marrow cell populations, and what are their relative contributions to bone marrow fibrosis remain unclear. From a drug development perspective, these works bring new cellular targets for bone marrow fibrosis.
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